Lipid metabolism. Lipid metabolism: symptoms of disorder and treatment methods

Lipid metabolism- fat metabolism that takes place in the organs of the digestive tract with the participation of enzymes produced by the pancreas. If this process is disrupted, symptoms may vary depending on the nature of the failure - an increase or decrease in lipid levels. With this dysfunction, the amount of lipoproteins is examined, since they can identify the risk of developing cardiovascular diseases. Treatment is determined strictly by the doctor based on the results obtained.

What is lipid metabolism?

When entering the body along with food, fats undergo primary processing in the stomach. However, complete digestion does not occur in this environment, since it is highly acidic but lacks bile acids.

Lipid metabolism scheme

When they enter the duodenum, which contains bile acids, the lipids undergo emulsification. This process can be described as partial mixing with water. Since the environment in the intestines is slightly alkaline, the acidic contents of the stomach are loosened under the influence of released gas bubbles, which are a product of the neutralization reaction.

The pancreas synthesizes a specific enzyme called lipase. It is he who acts on fat molecules, splitting them into two components: fatty acids and glycerin. Typically, fats are transformed into polyglycerides and monoglycerides.

Subsequently, these substances enter the epithelium of the intestinal wall, where the biosynthesis of lipids necessary for the human body occurs. They then combine with proteins to form chylomicrons (a class of lipoproteins), after which they are distributed throughout the body along with the flow of lymph and blood.

In the tissues of the body, the reverse process of obtaining fats from chylomicrons in the blood occurs. The most active biosynthesis occurs in the fat layer and liver.

Symptoms of a disrupted process

If lipid metabolism is disturbed in the human body, the result is various diseases with characteristic external and internal signs. The problem can only be identified after laboratory tests.

Impaired fat metabolism can manifest itself in the following symptoms of elevated lipid levels:

• the appearance of fatty deposits in the corners of the eyes;
• increased volume of the liver and spleen;
• increased body mass index;
• manifestations characteristic of nephrosis, atherosclerosis, endocrine diseases;
• increased vascular tone;
• formation of xanthomas and xanthelasmas of any localization on the skin and tendons. The first are nodular neoplasms containing cholesterol. They affect the palms, feet, chest, face and shoulders. The second group also represents cholesterol neoplasms, which have a yellow tint and appear on other areas of the skin.

When lipid levels are low, the following symptoms appear:

• weight loss;
• separation of the nail plates;
• hair loss;
• nephrosis;
• violation menstrual cycle and reproductive functions in women.

Lipidogram

Cholesterol moves in the blood along with proteins. There are several types of lipid complexes:

1. 1. Low-density lipoproteins (LDL). They are the most harmful fraction of lipids in the blood, with a high ability to form atherosclerotic plaques.
2. 2. High density lipoproteins (HDL). They have the opposite effect, preventing the formation of deposits. They transport free cholesterol to liver cells, where it is subsequently processed.
3. 3. Very low density lipoproteins (VLDL). They are the same harmful atherogenic compounds as LDL.
4. 4. Triglycerides. They are fatty compounds that are a source of energy for cells. When they are excessive in the blood, the vessels are predisposed to atherosclerosis.

Assessing the risk of developing cardiovascular diseases by cholesterol levels is not effective if a person has a disorder of lipid metabolism. With a predominance of atherogenic fractions over conditionally harmless ones (HDL), even with normal cholesterol levels, the likelihood of developing atherosclerosis seriously increases. Therefore, if fat metabolism is disturbed, a lipid profile should be performed, that is, blood biochemistry (analysis) should be performed to determine the amount of lipids.

Based on the obtained indicators, the atherogenicity coefficient is calculated. It shows the ratio of atherogenic lipoproteins to non-atherogenic ones. Defined as follows:

Formula for calculating the atherogenic coefficient

Normally, KA should be less than 3. If it is between 3 and 4, then there is a high risk of developing atherosclerosis. When the value exceeds 4, disease progression is observed.

Content

Fats, proteins and carbohydrates coming from food are processed into small components, which subsequently take part in metabolism, accumulate in the body or are used to produce energy necessary for normal life. An imbalance in the lipid transformation of fats is fraught with the development of serious complications and may be one of the causes of diseases such as atherosclerosis, diabetes mellitus, and myocardial infarction.

General characteristics of lipid metabolism

A person's daily need for fat is about 70-80 grams. The body receives most of the substances through food (exogenous route), the rest is produced by the liver (endogenous route). Lipid metabolism is the process by which fats are broken down into acids needed to generate energy or store energy sources for later use.

Fatty acids, also known as lipids, constantly circulate in the human body. According to their structure and principle of action, these substances are divided into several groups:

• Triacylglycerols make up the bulk of lipids in the body. They protect subcutaneous tissues and internal organs, acting as thermal insulators and heat retainers. Triacylglycerols are always stored by the body in reserve, as an alternative source of energy, in case of shortage of glycogen reserves (a form of carbohydrates obtained by processing glucose).
• Phospholipids are a large class of lipids that get their name from phosphoric acid. These substances form the basis of cell membranes and take part in the metabolic processes of the body.
• Steroids or cholesterols are an important component of cell membranes and are involved in energy, water-salt metabolism, regulate sexual functions.

The diversity and level of content of certain types of lipids in the cells of the body is regulated by lipid metabolism, which includes the following stages:

• Breakdown, digestion and absorption of substances in digestive tract(lipolysis). These processes originate in the oral cavity, where dietary fats, under the action of tongue lipase, break down into simpler compounds with the formation of fatty acids, monoacylglycerols and glycerol. In fact, the smallest droplets of fat, under the influence of special enzymes, are transformed into a thin emulsion, which is characterized by a lower density and an increased absorption area.
• Transport of fatty acids from the intestine to lymphatic system. After initial processing, all substances enter the intestine, where, under the action of bile acids and enzymes, they break down into phospholipids. New substances easily penetrate through the intestinal walls into the lymphatic system. Here they are again converted into triacylglycerols, bind to chylomicrons (molecules similar to cholesterol and better known as lipoproteins) and enter the blood. Lipoproteins interact with cell receptors, which break down these compounds and take the fatty acids necessary for energy production and membrane construction.
• Interconversion (catabolism) of fatty acids and ketone bodies. In fact, this is the final stage of lipid metabolism, during which some of the triacylglycerols are transported along with the blood to the liver, where they are converted into acetyl coenzyme A (abbreviated as acetyl CoA). If, as a result of the synthesis of fatty acids in the liver, acetyl CoA is released in excess, part of it is transformed into ketone bodies.
• Lipogenesis. If a person leads a sedentary lifestyle and receives fat in excess, some of the breakdown products of lipid metabolism are deposited in the form of adipocytes (adipose tissue). They will be used by organisms in case of energy shortage or when additional material is needed to build new membranes.

Signs of lipid metabolism disorders

Congenital or acquired pathology of fat metabolism in medicine is called dyslipidemia(ICD code E78). Often this disease is accompanied by a number of symptoms reminiscent of atherosclerosis (a chronic disease of the arteries, characterized by a decrease in their tone and elasticity), nephrosis (damage to the kidney tubules), diseases of the cardiovascular system. endocrine system. With high triglyceride levels, acute pancreatitis syndrome may occur. Characteristic clinical manifestations of lipid metabolism disorders are:

• Xanthomas are dense nodular formations filled with cholesterol. Cover the tendons, abdomen, and torso of the feet.
• Xanthelasmas are cholesterol deposits under the skin of the eyelids. Fatty deposits of this type are localized in the corners of the eyes.
• The lipoid arc is a white or grayish-white stripe framing the cornea of ​​the eye. More often, the symptom appears in patients over 50 years of age with a hereditary predisposition to dyslipidemia.
• Hepatosplenomegaly is a condition of the body in which the liver and spleen simultaneously increase in size.
• Skin atheroma is a cyst of the sebaceous glands that occurs as a result of blockage of the sebaceous ducts. One of the factors in the development of pathology is a disorder of phospholipid metabolism.
• Abdominal obesity is an excess accumulation of fatty tissue in the upper torso or abdomen.
• Hyperglycemia is a condition in which the level of glucose in the blood increases.
• Arterial hypertension – persistent increase blood pressure over 140/90 mm Hg. Art.

All of the above symptoms are characteristic of elevated lipid levels in the body. However, there are situations when the amount of fatty acids is below normal. In such cases characteristic symptoms will be:

• a sharp and causeless decrease in body weight, up to complete exhaustion (anorexia);
• hair loss, brittleness and splitting of nails;
• menstrual irregularities (delay or complete absence menstruation), reproductive system in women;
• signs of kidney nephrosis - darkening of urine, pain in the lower back, decreased volume of daily urine, formation of edema;
• eczema, pustules or other inflammations of the skin.

Reasons

Lipid metabolism can be impaired as a result of some chronic diseases or be congenital. According to the mechanism of formation pathological process there are two groups possible reasons dyslipidemia:

• Primary - inheritance from one or both parents of a modified gene. There are two forms of genetic disorders:

1. hypercholesterolemia – a disorder of cholesterol metabolism;
2. hypertriglyceridemia – increased content of triglycerides in blood plasma taken on an empty stomach.

• Secondary – the disease develops as a complication of other pathologies. Lipid metabolism disorders can be caused by:

1. hypothyroidism – decreased function thyroid gland;
2. diabetes mellitus is a disease in which glucose absorption or insulin production is impaired;
3. obstructive liver diseases - diseases in which there is a violation of the outflow of bile (chronic cholelithiasis (formation of stones in gallbladder), primary biliary cirrhosis (autoimmune disease, in which the intrahepatic bile ducts are gradually destroyed).
4. atherosclerosis;
5. obesity;
6. uncontrolled reception medicines– thiazide diuretics, Cyclosporine, Amiodarone, some hormonal contraceptives;
7. chronic renal failure– syndrome of impairment of all renal functions;
8. nephrotic syndrome is a symptom complex characterized by massive proteinuria (protein excretion along with urine), generalized edema;
9. radiation sickness is a pathology that occurs during prolonged exposure of the human body to various ionizing radiation;
10. pancreatitis - inflammation of the pancreas;
11. smoking, alcohol abuse.

Predisposing factors play an important role in the development and progression of lipid metabolism disorders. These include:

• physical inactivity (sedentary lifestyle);
• postmenopause;
• abuse of fatty, cholesterol-rich foods;
• arterial hypertension;
• male gender and age over 45 years;
• Cushing's syndrome - excessive production of adrenal hormones;
• history of ischemic stroke (death of a part of the brain due to circulatory problems);
• myocardial infarction (death of part of the heart muscle due to cessation of blood flow to it);
• genetic predisposition;
• pregnancy;
• previously diagnosed diseases of the endocrine system, liver or kidneys.

Classification

Depending on the mechanism of development, there are several types of lipid balance disorders:

• Primary (congenital) - means that the pathology is hereditary. Clinicians divide this type of lipid metabolism disorder into three forms:

1. monogenic – when the pathology is caused by gene mutations;
2. homozygous - a rare form, which means that the child received the pathological gene from both parents;
3. heterozygous - receiving a defective gene from the father or mother.

• Secondary (acquired) – develops as a consequence of other diseases.

• Nutritional – related to human nutritional characteristics. There are two forms of pathology:

1. transient – ​​occurs irregularly, more often on the next day after consuming a large amount fatty foods;
2. constant – observed with regular consumption of products with high content fat

Fredrickson classification of dyslipidemias was not received widespread among doctors, but is used by the World Health Organization. The main factor by which lipid metabolism disorders are divided into classes is the type of elevated lipid:

• The disease of the first type occurs due to genetic disorders. An increased content of chylomicrons is observed in the patient's blood.
• Type 2 lipid metabolism disorder is a hereditary pathology characterized by hypercholesterolemia (subtype A) or combined hyperlipidemia (subtype B).
• The third type is a pathological condition in which there is an absence of chylomicrons in the patient’s blood and the presence of low-density lipoproteins.
• The fourth type of disorder is hyperlipidemia (abnormally increased level lipids) of endogenous origin (produced by the liver).
• The fifth type is hypertriglyceridemia, characterized by an increased content of triglycerides in the blood plasma.

Doctors summarized this classification, reducing it to just two points. These include:

• pure or isolated hypercholesterolemia – a condition characterized by increased cholesterol levels;
• combined or mixed hyperlipidemia is a pathology in which the level of both triglycerides and cholesterol and other components of fatty acids increases.

Possible complications

Disorders of lipid metabolism can lead to a number of unpleasant symptoms, severe weight loss, and worsening of chronic diseases. Besides, This pathology in metabolic syndrome can cause the development of the following diseases and conditions:

• atherosclerosis, which affects the blood vessels of the heart, kidneys, brain, heart;
• narrowing of the lumen of blood arteries;
• formation of blood clots and emboli;
• the occurrence of an aneurysm (vascular dissection) or rupture of arteries.

Diagnostics

To make an initial diagnosis, the doctor conducts a thorough physical examination: assesses the condition of the skin, mucous membranes of the eye, measures blood pressure, palpation abdominal cavity. Afterwards, laboratory tests are prescribed to confirm or refute suspicions, which include:

• General clinical analysis of blood and urine. Conducted to identify inflammatory diseases.
• Biochemical blood test. Biochemistry determines the level of blood sugar, protein, creatinine (a breakdown product of protein), uric acid (the end product of the breakdown of DNA and RNA nucleotides).
• Lipidogram - analysis of lipids, is the main method for diagnosing lipid metabolism disorders. Diagnostics shows the level of cholesterol, triglycerides in the blood and establishes the atherogenicity coefficient (the ratio of the total amount of lipids to cholesterol).
• Immunological blood test. Determines the presence of antibodies (special proteins that are produced by the body to fight foreign bodies) to chlamydia and cytomegalovirus. An immunological test additionally detects the level of C-reactive protein (a protein that appears during inflammation).
• Genetic blood test. The study identifies inherited genes that have been damaged. Blood for diagnosis is necessarily taken from the patient himself and his parents.
• CT (computed tomography), ultrasound ( ultrasound examination) abdominal organs. They identify pathologies of the liver, spleen, pancreas, and help assess the condition of the organs.
• MRI (magnetic resonance imaging), radiography. They are prescribed as additional instrumental diagnostic methods when there is a suspicion of problems with the brain or lungs.

Treatment of fat metabolism disorders

To eliminate the pathology, patients are prescribed a special diet with a limited intake of animal fats, but enriched with dietary fiber and minerals. In overweight people, the daily caloric intake is reduced and moderate amounts are prescribed. physical activity necessary to normalize body weight. All patients are advised to give up or reduce alcohol consumption as much as possible. When treating secondary dyslipidemias, it is important to identify and begin treatment of the underlying disease.

To normalize the blood count and the patient’s condition, drug therapy. Eliminate unpleasant symptoms, the following groups of drugs help to establish lipid metabolism:

• Statins are a class of drugs that help lower blood levels. bad cholesterol, increase the possibility of lipid destruction. Medicines from this group are used for the treatment and prevention of atherosclerosis and diabetes mellitus. They significantly improve the patient’s quality of life, reduce the incidence of heart disease, and prevent vascular damage. Statins can cause liver damage and are therefore contraindicated in people with liver problems. These medications include:

1. Pravachol;
2. Zokor;
3. Crestor;
4. Lipitor;
5. Leskol.

• Cholesterol absorption inhibitors are a group of medications that prevent the reabsorption of cholesterol in the intestine. The effect of these drugs is limited, because a person receives only a fifth of bad cholesterol from food, the rest is produced in the liver. Inhibitors are prohibited for pregnant women, children, and during lactation. Popular medications in this group include:

1. Guarem;
2. Ezetimibe;
3. Lipobon;
4. Ezetrol.

• Bile acid sequestrants (ion exchange resins) are a group of medications that bind bile acids (containing cholesterol) when they enter the intestinal lumen and remove them from the body. With long-term use, sequestrants can cause constipation, taste disturbances, and flatulence. These include drugs with the following trade names:

1. Questran;
2. Colestipol;
3. Lipantil 200 M;
4. Tribestan.

• Antioxidant vitamins and Omega-3 polyunsaturated fatty acids are a group of multivitamin complexes that reduce triglyceride levels and reduce the risk of developing cardiovascular diseases. Such additives include:

1. Vitrum Cardio Omega-3;
2. ViaVit;
3. Mirrolla capsules with Omega-3;
4. AspaCardio.

• Fibrates – group medicines, reducing triglycerides and increasing the amount of high-density lipoproteins (protective substances that prevent the development of cardiovascular disorders). Medicines in this category are prescribed together with statins. Fibrates are not recommended for use by children or pregnant women. These include:

1. Normolit;
2. Lipantil;
3. Lipanor;
4. Bezalip;
5. Gevilon.

Diet therapy

Lipid metabolism in the human body directly depends on what he eats. A properly formulated diet will alleviate the patient’s condition and help restore metabolic balance. Detailed menu, the list of prohibited and permitted products is compiled by a doctor, but there are also general rules regarding nutrition:

1. Eat no more than 3 egg yolks per week (including eggs used for other food preparations).
2. Reducing the consumption of confectionery products, bread, and baked goods.
3. Replacing deep frying with stewing, steaming, boiling or baking.
4. Exclusion from the diet of smoked meats, marinades, sauces (mayonnaise, ketchup), sausages.
5. Increase in soto
6. proper consumption of plant fiber (vegetables and fruits).
7. There are only lean meats. When cooking, cut off visible fat and skin, remove rendered fat when preparing dishes.

Treatment with folk remedies

Drugs can be used as adjuvant therapy traditional medicine: decoctions, alcohol tinctures, infusions. For lipid metabolism disorders, the following recipes have proven themselves to be effective:

1. Mix and grind 100 grams of the following herbs using a coffee grinder: chamomile, knotweed, birch buds, immortelle, St. John's wort. Measure 15 grams of the mixture, pour 500 ml of boiling water. Insist for half an hour. Take the medicine warm, adding a teaspoon of honey, 200 ml in the morning and evening. Every day you should prepare a new drink. Store the remaining mixture in a dark place. Duration of therapy is 2 weeks.
2. Measure out 30 g of fireweed tea, pour 500 ml of boiling water over the herb. Bring the mixture to a boil over low heat, then leave for 30 minutes. Take the medicine 4 times a day before meals, 70 ml. The course of treatment is 3 weeks.
3. Pour dried plantain leaves (40 grams) with a glass of boiling water. Leave for 30 minutes, then filter. Take 30 ml of the drink 3 times a day 30 minutes before meals. The course of therapy is 3 weeks.

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The site provides background information for informational purposes only. Diagnosis and treatment of diseases must be carried out under the supervision of a specialist. All drugs have contraindications. Consultation with a specialist is required!

What kind of substances are lipids?

Lipids represent one of the groups of organic compounds that are of great importance for living organisms. By chemical structure All lipids are divided into simple and complex. Simple lipids are made up of alcohol and bile acids, while complex lipids also contain other atoms or compounds.

In general, lipids are of great importance to humans. These substances are included in a significant part of food products, are used in medicine and pharmacy, and play an important role in many industries. In a living organism, lipids in one form or another are part of all cells. From a nutritional point of view, it is a very important source of energy.

What is the difference between lipids and fats?

Basically, the term "lipids" comes from a Greek root meaning "fat", but there are still some differences between these definitions. Lipids are a larger group of substances, while fats refer to only certain types of lipids. A synonym for “fats” are “triglycerides,” which are obtained from a combination of glycerol alcohol and carboxylic acids. Both lipids in general and triglycerides in particular play a significant role in biological processes.

Lipids in the human body

Lipids are part of almost all tissues of the body. Their molecules are present in any living cell, and without these substances life is simply impossible. There are many different lipids found in the human body. Each type or class of these compounds has its own functions. Many biological processes depend on the normal supply and formation of lipids.

From a biochemical point of view, lipids take part in the following important processes:

• energy production by the body;

• cell division;
• transmission of nerve impulses;
• formation of blood components, hormones and other important substances;
• protection and fixation of some internal organs;
• cell division, respiration, etc.

Thus lipids are vital chemical compounds. A significant portion of these substances enters the body with food. After this, the structural components of lipids are absorbed by the body, and the cells produce new lipid molecules.

Biological role of lipids in a living cell

Lipid molecules perform huge amount functions not only on the scale of the entire organism, but also in each living cell individually. Essentially, a cell is structural unit living organism. It is where assimilation and synthesis occurs ( education) certain substances. Some of these substances go to maintaining the life of the cell itself, some to cell division, and some to the needs of other cells and tissues.

In a living organism, lipids perform the following functions:

• energy;
• reserve;
• structural;
• transport;
• enzymatic;
• storing;
• signal;
• regulatory

Energy function

The energy function of lipids is reduced to their breakdown in the body, during which a large amount of energy is released. Living cells need this energy to maintain various processes ( respiration, growth, division, synthesis of new substances). Lipids enter the cell with blood flow and are deposited inside ( in the cytoplasm) in the form of small drops of fat. If necessary, these molecules are broken down and the cell receives energy.

Reserve ( storing) function

The reserve function is closely related to the energy function. In the form of fats inside cells, energy can be stored “in reserve” and released as needed. Special cells – adipocytes – are responsible for the accumulation of fats. Most of their volume is occupied by a large drop of fat. It is adipocytes that make up adipose tissue in the body. The largest reserves of adipose tissue are located in the subcutaneous fat, the greater and lesser omentum ( in the abdominal cavity). During prolonged fasting, adipose tissue gradually breaks down, as lipid reserves are used to obtain energy.

Also, adipose tissue deposited in subcutaneous fat provides thermal insulation. Tissues rich in lipids are generally poorer conductors of heat. This allows the body to maintain a constant body temperature and not cool down or overheat so quickly. different conditions external environment.

Structural and barrier functions ( membrane lipids)

Lipids play a huge role in the structure of living cells. In the human body, these substances form a special double layer that forms the cell wall. Thanks to this, a living cell can perform its functions and regulate metabolism with the external environment. Lipids that form the cell membrane also help maintain the shape of the cell.

Why do lipid monomers form a double layer ( bilayer)?

Monomers are chemical substances ( in this case – molecules), which are capable of combining to form more complex compounds. The cell wall consists of a double layer ( bilayer) lipids. Each molecule that forms this wall has two parts - hydrophobic ( not in contact with water) and hydrophilic ( in contact with water). The double layer is obtained due to the fact that the lipid molecules are deployed with hydrophilic parts inside and outside the cell. The hydrophobic parts practically touch, as they are located between the two layers. Other molecules may also be located in the depth of the lipid bilayer ( proteins, carbohydrates, complex molecular structures), which regulate the passage of substances through the cell wall.

Transport function

The transport function of lipids is of secondary importance in the body. Only some connections do this. For example, lipoproteins, consisting of lipids and proteins, transport certain substances in the blood from one organ to another. However, this function is rarely isolated, without considering it to be the main one for these substances.

Enzymatic function

In principle, lipids are not part of the enzymes involved in the breakdown of other substances. However, without lipids, organ cells will not be able to synthesize enzymes, the end product of vital activity. In addition, some lipids play a significant role in the absorption of dietary fats. Bile contains significant amounts of phospholipids and cholesterol. They neutralize excess pancreatic enzymes and prevent them from damaging intestinal cells. Dissolution also occurs in bile ( emulsification) exogenous lipids coming from food. Thus, lipids play a huge role in digestion and help in the work of other enzymes, although they are not enzymes themselves.

Signal function

Some complex lipids perform a signaling function in the body. It consists of maintaining various processes. For example, glycolipids in nerve cells take part in the transmission of nerve impulses from one nerve cell to another. In addition, signals within the cell itself are of great importance. She needs to “recognize” substances entering the blood in order to transport them inside.

Regulatory function

The regulatory function of lipids in the body is secondary. The lipids themselves in the blood have little effect on the course of various processes. However, they are part of other substances that are of great importance in the regulation of these processes. First of all, these are steroid hormones ( adrenal hormones and sex hormones). They play an important role in metabolism, growth and development of the body, reproductive function, affect work immune system. Lipids are also part of prostaglandins. These substances are produced during inflammatory processes and affect some processes in nervous system (for example, pain perception).

Thus, lipids themselves do not perform a regulatory function, but their deficiency can affect many processes in the body.

Biochemistry of lipids and their relationship with other substances ( proteins, carbohydrates, ATP, nucleic acids, amino acids, steroids)

Lipid metabolism is closely related to the metabolism of other substances in the body. First of all, this connection can be traced in human nutrition. Any food consists of proteins, carbohydrates and lipids, which must enter the body in certain proportions. In this case, a person will receive both enough energy and enough structural elements. Otherwise ( for example, with a lack of lipids) proteins and carbohydrates will be broken down to produce energy.

Also, lipids are, to one degree or another, associated with the metabolism of the following substances:

• Adenosine triphosphoric acid ( ATP). ATP is a unique unit of energy inside a cell. When lipids are broken down, part of the energy goes into the production of ATP molecules, and these molecules take part in all intracellular processes ( transport of substances, cell division, neutralization of toxins, etc.).
• Nucleic acids. Nucleic acids are structural elements of DNA and are found in the nuclei of living cells. The energy generated during the breakdown of fats is partially used for cell division. During division, new DNA chains are formed from nucleic acids.
• Amino acids. Amino acids are structural components of proteins. In combination with lipids, they form complex complexes, lipoproteins, responsible for the transport of substances in the body.
• Steroids. Steroids are a type of hormone that contains significant amounts of lipids. If lipids from food are poorly absorbed, the patient may experience problems with the endocrine system.

Thus, lipid metabolism in the body in any case must be considered in its entirety, from the point of view of its relationship with other substances.

Digestion and absorption of lipids ( metabolism, metabolism)

Digestion and absorption of lipids is the first stage in the metabolism of these substances. The main part of lipids enters the body with food. In the oral cavity, food is crushed and mixed with saliva. Next, the lump enters the stomach, where the chemical bonds are partially destroyed by hydrochloric acid. Also, some chemical bonds in lipids are destroyed by the enzyme lipase contained in saliva.

Lipids are insoluble in water, so they are not immediately broken down by enzymes in the duodenum. First, the so-called emulsification of fats occurs. After this, the chemical bonds are broken down by lipase coming from the pancreas. In principle, each type of lipid now has its own enzyme responsible for the breakdown and absorption of this substance. For example, phospholipase breaks down phospholipids, cholesterol esterase breaks down cholesterol compounds, etc. All these enzymes are contained in varying quantities in pancreatic juice.

Cleaved lipid fragments are individually absorbed by cells small intestine. In general, fat digestion is a very complex process that is regulated by many hormones and hormone-like substances.

What is lipid emulsification?

Emulsification is the incomplete dissolution of fatty substances in water. In the bolus of food entering the duodenum, fats are contained in the form of large droplets. This prevents them from interacting with enzymes. During the emulsification process, large fat droplets are “crushed” into smaller droplets. As a result, the contact area between fat droplets and surrounding water-soluble substances increases, and lipid breakdown becomes possible.

The process of emulsifying lipids into digestive system takes place in several stages:

• At the first stage, the liver produces bile, which will emulsify fats. It contains salts of cholesterol and phospholipids, which interact with lipids and contribute to their “crushing” into small droplets.
• Bile secreted from the liver accumulates in the gallbladder. Here it is concentrated and released as needed.
• When consuming fatty foods, a signal is sent to the smooth muscles of the gallbladder to contract. As a result, a portion of bile is released through the bile ducts into the duodenum.
• In the duodenum, fats are actually emulsified and interact with pancreatic enzymes. Contractions in the walls of the small intestine facilitate this process by “mixing” the contents.

Some people may have trouble absorbing fat after having their gallbladder removed. Bile enters the duodenum continuously, directly from the liver, and is not enough to emulsify the entire volume of lipids if too much is eaten.

Enzymes for lipid breakdown

To digest each substance, the body has its own enzymes. Their task is to break chemical bonds between molecules ( or between atoms in molecules), to useful substances could be normally absorbed by the body. Different enzymes are responsible for breaking down different lipids. Most of them are contained in the juice secreted by the pancreas.

The following groups of enzymes are responsible for the breakdown of lipids:

• lipases;
• phospholipases;
• cholesterol esterase, etc.

What vitamins and hormones are involved in the regulation of lipid levels?

The levels of most lipids in human blood are relatively constant. It can fluctuate within certain limits. This depends on the biological processes occurring in the body itself, and on a number of external factors. Regulation of blood lipid levels is a complex biological process in which many different organs and substances are involved.

The following substances play the greatest role in the absorption and maintenance of constant lipid levels:

• Enzymes. A number of pancreatic enzymes take part in the breakdown of lipids entering the body with food. With a lack of these enzymes, the level of lipids in the blood may decrease, since these substances simply will not be absorbed in the intestines.
• Bile acids and their salts. Bile contains bile acids and a number of their compounds, which contribute to the emulsification of lipids. Without these substances, normal absorption of lipids is also impossible.
• Vitamins. Vitamins have a complex strengthening effect on the body and directly or indirectly also affect lipid metabolism. For example, with a lack of vitamin A, cell regeneration in the mucous membranes deteriorates, and the digestion of substances in the intestines also slows down.
• Intracellular enzymes. The intestinal epithelial cells contain enzymes that, after absorption of fatty acids, convert them into transport forms and send them into the bloodstream.
• Hormones. A number of hormones affect metabolism in general. For example, high insulin levels can greatly affect blood lipid levels. That is why some standards have been revised for patients with diabetes. Thyroid hormones, glucocorticoid hormones, or norepinephrine can stimulate the breakdown of fat tissue to release energy.

Thus, maintaining normal level lipids in the blood is a very complex process, which is directly or indirectly influenced by various hormones, vitamins and other substances. During the diagnostic process, the doctor needs to determine at what stage this process was disrupted.

Biosynthesis ( education) and hydrolysis ( decay) lipids in the body ( anabolism and catabolism)

Metabolism is the totality of metabolic processes in the body. All metabolic processes can be divided into catabolic and anabolic. Catabolic processes include the breakdown and breakdown of substances. In relation to lipids, this is characterized by their hydrolysis ( breakdown into simpler substances) in the gastrointestinal tract. Anabolism combines biochemical reactions aimed at the formation of new, more complex substances.

Lipid biosynthesis occurs in the following tissues and cells:

• Intestinal epithelial cells. Absorption of fatty acids, cholesterol and other lipids occurs in the intestinal wall. Immediately after this, new transport forms of lipids are formed in the same cells, which enter the venous blood and go to the liver.
• Liver cells. In liver cells, some of the transport forms of lipids will disintegrate, and new substances are synthesized from them. For example, cholesterol and phospholipid compounds are formed here, which are then excreted in bile and contribute to normal digestion.
• Cells of other organs. Some lipids travel with the blood to other organs and tissues. Depending on the cell type, lipids are converted into a specific type of compound. All cells, one way or another, synthesize lipids to form the cell wall ( lipid bilayer). In the adrenal glands and gonads, steroid hormones are synthesized from some of the lipids.

The combination of the above processes constitutes lipid metabolism in the human body.

Resynthesis of lipids in the liver and other organs

Resynthesis is the process of formation of certain substances from simpler ones that were absorbed earlier. In the body, this process occurs in the internal environment of some cells. Resynthesis is necessary so that tissues and organs receive all the necessary types of lipids, and not just those consumed with food. Resynthesized lipids are called endogenous. The body spends energy on their formation.

At the first stage, lipid resynthesis occurs in the intestinal walls. Here, fatty acids ingested from food are converted into transport forms that are transported through the blood to the liver and other organs. Part of the resynthesized lipids will be delivered to the tissues; from the other part, substances necessary for life will be formed ( lipoproteins, bile, hormones, etc.), the excess is converted into adipose tissue and stored “in reserve.”

Are lipids part of the brain?

Lipids are a very important component of nerve cells, not only in the brain, but throughout the entire nervous system. As you know, nerve cells control various processes in the body by transmitting nerve impulses. In this case, all nerve pathways are “isolated” from each other so that the impulse comes to certain cells and does not affect other nerve pathways. This “isolation” is possible thanks to the myelin sheath of nerve cells. Myelin, which prevents the chaotic propagation of impulses, consists of approximately 75% lipids. As in cell membranes, here they form a double layer ( bilayer), which is wrapped several times around the nerve cell.

The myelin sheath in the nervous system contains the following lipids:

• phospholipids;
• cholesterol;
• galactolipids;
• glycolipids.

Some congenital lipid disorders may cause neurological problems. This is explained precisely by the thinning or interruption of the myelin sheath.

Lipid hormones

Lipids play an important structural role, including being present in the structure of many hormones. Hormones that contain fatty acids are called steroid hormones. In the body they are produced by the gonads and adrenal glands. Some of them are also present in adipose tissue cells. Steroid hormones take part in the regulation of many vital processes. Their imbalance can affect body weight, the ability to conceive a child, the development of any inflammatory processes, the functioning of the immune system. The key to normal production of steroid hormones is a balanced intake of lipids.

Lipids are part of the following vital hormones:

• corticosteroids ( cortisol, aldosterone, hydrocortisone, etc.);
• male sex hormones - androgens ( androstenedione, dihydrotestosterone, etc.);
• female sex hormones - estrogens ( estriol, estradiol, etc.).

Thus, a lack of certain fatty acids in food can seriously affect the functioning of the endocrine system.

The role of lipids for skin and hair

Lipids are of great importance for the health of the skin and its appendages ( hair and nails). The skin contains so-called sebaceous glands, which secrete a certain amount of secretion rich in fats onto the surface. This substance performs many useful functions.

Lipids are important for hair and skin for the following reasons:

• a significant part of the hair substance consists of complex lipids;
• skin cells change rapidly, and lipids are important as an energy resource;
• secret ( secreted substance) sebaceous glands moisturize the skin;
• Thanks to fats, the firmness, elasticity and smoothness of the skin is maintained;
• a small amount of lipids on the surface of the hair gives it a healthy shine;
• the lipid layer on the surface of the skin protects it from the aggressive effects of external factors ( cold, sun rays, microbes on the surface of the skin, etc.).

In skin cells, as in hair follicles, lipids enter the blood. Thus, proper nutrition ensures healthy skin and hair. The use of shampoos and creams containing lipids ( especially essential fatty acids) is also important because some of these substances will be absorbed from the surface of the cells.

Classification of lipids

In biology and chemistry, there are quite a few different classifications of lipids. The main one is the chemical classification, according to which lipids are divided depending on their structure. From this point of view, all lipids can be divided into simple ones ( consisting only of oxygen, hydrogen and carbon atoms) and complex ( containing at least one atom of other elements). Each of these groups has corresponding subgroups. This classification is the most convenient, since it reflects not only the chemical structure of substances, but also partially determines the chemical properties.

Biology and medicine have their own additional classifications that use other criteria.

Exogenous and endogenous lipids

All lipids in the human body can be divided into two large groups - exogenous and endogenous. The first group includes all substances that enter the body from the external environment. The largest amount of exogenous lipids enters the body with food, but there are other routes. For example, when using various cosmetics or medications, the body may also receive some lipids. Their action will be predominantly local.

After entering the body, all exogenous lipids are broken down and absorbed by living cells. Here, from their structural components, other lipid compounds that the body needs will be formed. These lipids, synthesized by one's own cells, are called endogenous. They may have a completely different structure and function, but they consist of the same “structural components” that entered the body with exogenous lipids. That is why, with a lack of certain types of fats in food, various diseases can develop. Some components of complex lipids cannot be synthesized by the body independently, which affects the course of certain biological processes.

Fatty acids

Fatty acids are a class of organic compounds that are a structural part of lipids. Depending on which fatty acids are included in the lipid, the properties of this substance may change. For example, triglycerides, the most important source of energy for the human body, are derivatives of the alcohol glycerol and several fatty acids.

In nature, fatty acids are found in a variety of substances - from oil to vegetable oils. They enter the human body mainly through food. Each acid is a structural component for specific cells, enzymes or compounds. Once absorbed, the body converts it and uses it in various biological processes.

The most important sources of fatty acids for humans are:

• animal fats;
• vegetable fats;
• tropical oils ( citrus, palm, etc.);
• fats for the food industry ( margarine, etc.).

In the human body, fatty acids can be stored in adipose tissue as triglycerides or circulate in the blood. They are found in the blood both in free form and in the form of compounds ( various fractions of lipoproteins).

Saturated and unsaturated fatty acids

All fatty acids according to their chemical structure are divided into saturated and unsaturated. Saturated acids are less beneficial for the body, and some of them are even harmful. This is explained by the fact that there are no double bonds in the molecule of these substances. These are chemically stable compounds and are less easily absorbed by the body. Currently, the connection between some saturated fatty acids and the development of atherosclerosis has been proven.

Unsaturated fatty acids are divided into two large groups:

• Monounsaturated. These acids have one double bond in their structure and are therefore more active. It is believed that eating them can lower cholesterol levels and prevent the development of atherosclerosis. The greatest amount of monounsaturated fatty acids is found in a number of plants ( avocado, olives, pistachios, hazelnuts) and, accordingly, in oils obtained from these plants.
• Polyunsaturated. Polyunsaturated fatty acids have several double bonds in their structure. Distinctive feature of these substances is that the human body is not able to synthesize them. In other words, if the body does not receive polyunsaturated fatty acids from food, over time this will inevitably lead to certain disorders. The best sources of these acids are seafood, soybean and flaxseed oil, sesame seeds, poppy seeds, wheat germ, etc.

Phospholipids

Phospholipids are complex lipids containing a phosphoric acid residue. These substances, along with cholesterol, are the main components of cell membranes. These substances also take part in the transport of other lipids in the body. From a medical point of view, phospholipids can also play a signaling role. For example, they are part of bile, as they promote emulsification ( dissolution) other fats. Depending on which substance is more in bile, cholesterol or phospholipids, you can determine the risk of developing cholelithiasis.

Glycerol and triglycerides

In terms of its chemical structure, glycerol is not a lipid, but it is an important structural component of triglycerides. This is a group of lipids that play a huge role in the human body. The most important function of these substances is to supply energy. Triglycerides that enter the body with food are broken down into glycerol and fatty acids. As a result, a very large amount of energy is released, which goes to work the muscles ( skeletal muscles, cardiac muscles, etc.).

Adipose tissue in the human body is represented mainly by triglycerides. Most of these substances, before being deposited in adipose tissue, undergo some chemical transformations in the liver.

Beta lipids

Beta lipids are sometimes called beta lipoproteins. The duality of the name is explained by differences in classifications. This is one of the fractions of lipoproteins in the body, which plays an important role in the development of certain pathologies. First of all, we're talking about about atherosclerosis. Beta lipoproteins transport cholesterol from one cell to another, but due to the structural features of the molecules, this cholesterol often “gets stuck” in the walls of blood vessels, forming atherosclerotic plaques and preventing normal blood flow. Before use, you should consult a specialist.

Constant turmoil, dry food, passion for semi-finished products - characteristic feature modern society. As a rule, an unhealthy lifestyle leads to weight gain. In such cases, doctors often state that a person’s lipid metabolism is disturbed. Of course, many people do not have such specific knowledge and have no idea what lipid metabolism is.

What are lipids?

Meanwhile, lipids are present in every living cell. These biological molecules, which are organic substances, have in common physical property– insolubility in water (hydrophobicity). Lipids are made up of various chemicals, but most of them are fats. The human body is so wisely designed that it is able to synthesize most of the fats on its own. But essential fatty acids (for example, linoleic acid) must enter the body from the outside through food. Lipid metabolism occurs at the cellular level. This is a rather complex physiological and biochemical process, consisting of several stages. First, lipids are broken down, then absorbed, after which intermediate and final exchange occurs.

Split

In order for the body to absorb lipids, they must first be broken down. First, food that contains lipids enters the oral cavity. There it is moistened with saliva, mixed, crushed and forms a food mass. This mass enters the esophagus, and from there into the stomach, where it is saturated with gastric juice. In turn, the pancreas produces lipase, a lipolytic enzyme that is capable of breaking down emulsified fats (that is, fats mixed with a liquid medium). Then the semi-liquid food mass enters the duodenum, then the ileum and jejunum, where the splitting process ends. Thus, pancreatic juice, bile and gastric juice are involved in the breakdown of lipids.

Suction

After splitting, the process of lipid absorption begins, which mainly occurs in the upper part of the small intestine and the lower part duodenum. There are no lipolytic enzymes in the large intestine. The products formed after the breakdown of lipids are glycerophosphates, glycerol, higher fatty acids, monoglycerides, diglycerides, cholesterol, nitrogenous compounds, phosphoric acid, higher alcohols and small fat particles. All these substances are absorbed by the epithelium of the intestinal villi.

Intermediate and final exchange

Intermediate metabolism is a combination of several very complex biochemical processes, among which it is worth highlighting the conversion of triglycerides into higher fatty acids and glycerol. The final stage of intermediate metabolism is the metabolism of glycerol, the oxidation of fatty acids and the biological synthesis of other lipids.

At the last stage of metabolism, each group of lipids has its own specificity, but the main products of final metabolism are water and carbon dioxide. Water leaves the body naturally, through sweat and urine, and carbon dioxide through the lungs when exhaling air. This completes the process of lipid metabolism.

Lipid metabolism disorder

Any disorder in the process of fat absorption indicates a disorder in lipid metabolism. This may be due to insufficient intake of pancreatic lipase or bile into the intestine, as well as hypovitaminosis, obesity, atherosclerosis, various diseases gastrointestinal tract and others pathological conditions. When the villous epithelial tissue in the intestine is damaged, fatty acids are no longer fully absorbed. As a result, in stool A large amount of undigested fat accumulates. The stool takes on a characteristic whitish-gray color.

Of course, with the help of diet and medications that lower cholesterol levels, it is possible to correct and improve the process of lipid metabolism. You will need to regularly monitor the concentration of triglycerides in your blood. However, it should be remembered that the human body only needs a small amount of fat. To prevent lipid metabolism disorders, you should reduce the consumption of meat, oil, offal and give preference to fish and seafood. Lead active image life, move more, adjust your weight. Be healthy!

Lipid metabolism is the metabolism of lipids; it is a complex physiological and biochemical process that occurs in the cells of living organisms. Neutral lipids such as cholesterol and triglycerides (TG) are insoluble in plasma. As a result, lipids circulating in the blood are attached to proteins that transport them to various tissues for energy utilization, deposition as adipose tissue, production of steroid hormones and formation of bile acids.

A lipoprotein is composed of a lipid (the esterified or non-esterified form of cholesterol, triglycerides and phospholipids) and a protein. The protein components of lipoprotein are known as apolipoproteins and apoproteins.

Features of fat metabolism

Lipid metabolism is divided into two main metabolic pathways: endogenous and exogenous. This division is based on the origin of the lipids in question. If the source of lipids is food, then we are talking about an exogenous metabolic pathway, and if the liver is an endogenous one.

There are different classes of lipids, each of which is characterized by a separate function. There are chylomicrons (CM), (VLDL), medium-density lipoproteins (MDLP), and density lipoproteins (HDL). The metabolism of individual classes of lipoproteins is not independent; they are all closely interrelated. Understanding lipid metabolism is important for an adequate understanding of the pathophysiology of cardiovascular diseases (CVD) and the mechanisms of action of drugs.

Cholesterol and triglycerides are required by peripheral tissues for a variety of aspects of homeostasis, including the maintenance of cell membranes, the synthesis of steroid hormones and bile acids, and energy utilization. Considering that lipids cannot dissolve in plasma, they are carried by various lipoproteins circulating in the circulatory system.

The basic structure of a lipoprotein usually includes a core consisting of esterified cholesterol and triglyceride, surrounded by a bilayer of phospholipids, as well as non-esterified cholesterol and various proteins called apolipoproteins. These lipoproteins differ in their size, density and composition of lipids, apolipoproteins and other characteristics. It is significant that lipoproteins have different functional qualities (Table 1).

Table 1. Indicators of lipid metabolism and physical characteristics of lipoproteins in plasma.

Lipoprotein	Lipid content	Apolipoproteins	Density (g/ml)	Diameter
Chylomicron (CM)	TG	A-l, A-ll, A-IV, B48, C-l, C-ll, C-IIL E	<0,95	800-5000
Residual chylomicron	TG, cholesterol ester	B48,E	<1,006	>500
VLDL	TG	B100, C-l, C-ll, C-IIL E	< 1,006	300-800
LPSP	Cholesterol ester, TG	B100, C-l, C-ll, C-l II, E	1,006-1,019	250-350
LDL	Cholesterol ester, TG	B100	1,019-1,063	180-280
HDL	Cholesterol ester, TG	A-l, A-ll, A-IV, C-l, C-ll, C-ll, D	1,063-1,21	50-120

The main classes of lipoproteins, ordered by decreasing particle size:

• VLDL,
• LPSP,
• LDL,
• HDL.

Dietary lipids enter the circulatory system by attaching to apolipoprotein (apo) B48, which contains chylomicrons synthesized in the intestine. The liver synthesizes VLDL1 and VLDL2 around apoB100, attracting lipids present in the circulatory system (free fatty acids) or in the diet (chylomicron remnants). VLDL1 and VLDL2 are then delipidated by lipoprotein lipase, releasing fatty acids for consumption by skeletal muscle and adipose tissue. VLDL1, releasing lipids, is converted into VLDL2, VLDL2 is further transformed into LPSP. Residual chylomicron, LPSP and LDL can be taken up by the liver through the receptor.

High-density lipoproteins are formed in the intercellular space, where apoAI contacts phospholipids, free cholesterol and forms a disc-shaped HDL particle. Next, this particle interacts with lecithin, and cholesterol esters are formed, forming the HDL core. Cholesterol is ultimately consumed by the liver, and apoAI is secreted by the intestine and liver.

The metabolic pathways of lipids and lipoproteins are closely interconnected. Despite the fact that there are a number of effective drugs that lower lipids in the body, their mechanism of action still remains poorly understood. Further clarification of the molecular mechanisms of action of these drugs is required to improve the quality of treatment of dyslipidemia.

Effect of drugs on lipid metabolism

• Statins increase the rate of elimination of VLDL, LPSP and LDL, and also reduce the intensity of VLDL synthesis. This ultimately improves the lipoprotein profile.
• Fibrates accelerate the clearance of apoB particles and intensify the production of apoAI.
• Nicotinic acid reduces LDL and TG, and also increases HDL content.
• Reducing body weight helps reduce the secretion of VLDL, which improves lipoprotein metabolism.
• The regulation of lipid metabolism is optimized by omega-3 fatty acids.

Genetic disorders

Science knows a whole set of hereditary dyslipidemic diseases, in which the main defect is the regulation of lipid metabolism. The hereditary nature of these diseases is in some cases confirmed by genetic studies. These diseases are often identified through early lipid screening.

A short list of genetic forms of dyslipidemia.

• Hypercholesterolemia: familial hypercholesterolemia, hereditary defective apoB100, polygenic hypercholesterolemia.
• Hypertriglyceridemia: familial hypertriglyceridemia, familial hyperchylomicronemia, lipoprotein lipase deficiency.
• Disturbances in HDL metabolism: familial hypoalphalipoproteinemia, LCAT deficiency, apoA-l point mutations, ABCA1 deficiency.
• Combined forms of hyperlipidemia: familial combined hyperlipidemia, hyperapobetalipoproteinemia, familial disbetalipoproteinemia.

Hypercholesterolemia

Familial hypercholesterolemia is a monozygotic, autosomal, dominant disease involving defective expression and functional activity of the LDL receptor. Heterozygous expression of this disease among the population is observed in one case out of five hundred. Various phenotypes have been identified based on defects in receptor synthesis, trafficking, and binding. This type of familial hypercholesterolemia is associated with significant elevations in LDL cholesterol, the presence of xanthomas, and the premature development of diffuse atherosclerosis.

Clinical manifestations are more pronounced in patients with homozygous mutations. Diagnosis of lipid metabolism disorders is often made on the basis of severe hypercholesterolemia with normal TG and the presence of tendon xanthomas, as well as in the presence of a family history of early CVD. Genetic methods are used to confirm the diagnosis. Treatment uses high doses of statins in addition to medications. In some cases, LDL apheresis is required. Additional evidence from recent research supports the use of intensive care for children and adolescents at high risk. Additional therapeutic options for complex cases include liver transplantation and gene replacement therapy.

Hereditary defective apoB100

Inherited defects in the apoB100 gene are an autosomal disorder that results in lipid abnormalities reminiscent of familial hypercholesterolemia. The clinical severity and approach to treatment of this disease are similar to those for heterozygous familial hypercholesterolemia. Polygenic cholesterolemia is characterized by a moderate increase in LDL, normal TG, early atherosclerosis and the absence of xanthoma. Defects including increased apoB synthesis and decreased receptor expression can lead to elevated LDL cholesterol.

Hypertriglyceridemia

Familial hypertriglyceridemia is an autosomal dominant disorder characterized by elevated triglycerides combined with insulin resistance and failure to regulate blood pressure and uric acid levels. Mutations in the lipoprotein lipase gene that underlie this disease are responsible for the extent of the rise in triglyceride levels.

Familial hyperchylomicronemia is an extensive form of lipoprotein lipase mutation leading to a more complex form of hypertriglyceridemia. Lipoprotein lipase deficiency is associated with hypertriglyceridemia and early atherosclerosis. This disease requires a reduction in fat intake and the use of drug therapy to reduce TG. It is also necessary to stop drinking alcohol, combat obesity and intensive treatment of diabetes.

Disturbances in the metabolism of high-density lipoproteins

Familial hypoalphalipoproteinemia is a rare autosomal disease involving mutations in the apoA-I gene and leading to a decrease in high-density lipoproteins and early atherosclerosis. Lecithin cholesterol acyltransferase deficiency is characterized by faulty esterification of cholesterol on the surface of HDL particles. The result is low HDL levels. Various genetic mutations of apoA-I involving single amino acid substitutions have been described in a number of cases.

Analphalipoproteinemia is characterized by the accumulation of cellular lipids and the presence of foam cells in peripheral tissues, as well as hepatosplenomegaly, peripheral neuropathy, low HDL levels and early atherosclerosis. This disease is caused by mutations in the ABCA1 gene, leading to cellular accumulation of cholesterol. Enhanced renal clearance of apoA-I contributes to the reduction of high-density lipoproteins.

Combined forms of hyperlipidemia

The incidence of familial combined hyperlipidemia can reach 2% in the population. It is characterized by elevated levels of apoB, LDL, and triglycerides. This disease is caused by excess synthesis of apoB100 in the liver. The severity of the disease in a particular individual is determined by the relative lack of lipoprotein lipase activity. Hyperbetalipoproteinemia is a type of familial hyperlipidemia. Statins are commonly used to treat this disease in combination with other drugs, including niacin, bile acid sequestrants, ezetimibe, and fibrates.

Familial dysbetalipoproteinemia is an autosomal recessive disorder characterized by the presence of two apoE2 alleles, as well as elevated LDL cholesterol, xanthomas, and early development of CVD. Failure in the clearance of VLDL and residual chylomicrons leads to the formation of VLDL particles (beta-VLDL). Since this disease is dangerous for the development of CVD and acute pancreatitis, intensive therapy is required to reduce triglycerides.

Lipid metabolism disorders - general characteristics

• Inherited diseases of lipoprotein homeostasis lead to hypercholesterolemia, hypertriglyceridemia and low HDL levels.
• In most of these cases, there is an increased risk of early CVD.
• Diagnosis of metabolic disorders includes early screening using lipidograms, which are an adequate measure for early detection of problems and initiation of therapy.
• For close relatives of patients, screening using lipid profiles is recommended, starting in early childhood.

Secondary causes contributing to lipid metabolism disorders

A small number of cases of abnormal LDL, TG, and HDL levels are caused by underlying medical problems and medications. Treatment of these causes usually leads to normalization of lipid metabolism. Accordingly, for patients with dyslipidemia, examination is required for the presence of secondary causes of lipid metabolism disorders.

Assessment of secondary causes of lipid metabolism disorders should be made during the initial examination. Analysis of the initial condition of patients with dyslipidemia should include an assessment of the thyroid gland, as well as liver enzymes, blood sugar and urine biochemistry parameters.

Lipid metabolism disorders in diabetes mellitus

Diabetes is accompanied by hypertriglyceridemia, low HDL and the presence of small and dense LDL particles. In this case, insulin resistance, obesity, increased levels of glucose and free fatty acids and decreased lipoprotein lipase activity are noted. Intensive glycemic control and reduction of central obesity may have a positive effect on total lipid levels, especially in the presence of hypertriglyceridemia.

Disturbances in glucose homeostasis observed in diabetes are accompanied by high blood pressure and dyslipidemia, which leads to atherosclerotic phenomena in the body. Ischemic heart disease is the most important factor in mortality in patients with diabetes mellitus. The incidence of this disease is 3–4 times higher in patients with non-insulin-dependent diabetes than in the norm. LDL-lowering drug therapy, especially statins, is effective in reducing the severity of CVD in diabetics.

Biliary obstruction

Chronic cholelithiasis and primary biliary cirrhosis are associated with hypercholesterolemia through the development of xanthomas and increased blood viscosity. Treatment of bile duct obstruction can help normalize lipid metabolism. Although standard lipid-lowering medications can usually be used for biliary obstruction, statins are generally contraindicated in patients with chronic liver disease or cholelithiasis. Plasmaphoresis can also be used to treat symptomatic xanthomas and hyperviscosity.

Kidney diseases

Hypertriglyceridemia is common in patients suffering from chronic renal failure. This is largely due to decreased lipoprotein lipase and hepatic lipase activity. Abnormal triglyceride levels are commonly observed in individuals undergoing peritoneal dialysis treatment.

It has been suggested that a reduced rate of elimination of potential lipase inhibitors plays a key role in the development of this process. There is also an increased level of lipoprotein (a) and a low level of HDL, which leads to an accelerated development of CVD. Secondary reasons contributing to the development of hypertriglyceridemia include:

• Diabetes mellitus
• Chronic renal failure
• Obesity
• Nephrotic syndrome
• Cushing's syndrome
• Lipodystrophy
• Tobacco smoking
• Excess carbohydrate intake

An attempt was made through clinical trials to elucidate the effects of lipid-lowering therapy in patients with end-stage renal disease. These studies showed that atorvastatin did not reduce the composite endpoint of CVD, myocardial infarction and stroke. It was also noted that rosuvastatin did not reduce the incidence of CVD in patients on regular hemodialysis.

Nephrotic syndrome is associated with increased TG and lipoprotein (a), which is caused by increased synthesis of apoB by the liver. Treatment of nephrotic syndrome is based on eliminating the underlying problems, as well as normalizing lipid levels. The use of standard lipid-lowering therapy can be effective, but constant monitoring for possible side effects is required.

Thyroid diseases

Hypothyroidism is accompanied by elevated levels of LDL and triglycerides, and the degree to which they deviate from normal depends on the extent of the problems with the thyroid gland. The reason for this is a decrease in the expression and activity of the LDL receptor, as well as a decrease in lipoprotein lipase activity. Hyperthyroidism usually manifests as low LDL and TG.

Obesity

Central obesity is accompanied by increased levels of VLDL and triglycerides, as well as low HDL. Weight loss, as well as dietary adjustments, lead to a positive effect on triglyceride and HDL levels.

Medicines

Many concomitant medications cause the development of dyslipidemia. For this reason, the initial evaluation of patients with lipid abnormalities should be accompanied by careful consideration of medications.
Table 2. Drugs that affect lipid levels.

Preparation	Increased LDL	Increased triglycerides	Decrease in HDL
Thiazide diuretics	+
Cyclosporine	+
Amiodarone	+
Rosiglitazone	+
Bile acid sequestrants		+
Proteinase inhibitors		+
Retinoids		+
Glucocorticoids		+
Anabolic steroid		+
Sirolimus		+
Beta blockers		+	+
Progestins			+
Androgens			+

Thiazide diuretics and beta blockers often cause hypertriglyceridemia and low HDL when taken. Exogenous estrogen and progesterone, which are part of the components of hormone replacement therapy and oral contraceptives, cause hypertriglyceridemia and a decrease in HDL. Antiretroviral drugs for HIV patients are accompanied by hypertriglyceridemia, increased LDL, insulin resistance and lipodystrophy. Anabolic steroids, corticosteroids, cyclosporine, tamoxifen and retinoids also lead to lipid metabolism abnormalities when used.

Treatment of lipid metabolism disorders

Correction of lipid metabolism

The role of lipids in the pathogenesis of atherosclerotic CVD has been well studied and substantiated. This has led to an active search for ways to reduce the level of atherogenic lipids and enhance the protective properties of HDL. The past five decades have been characterized by the development of a wide range of dietary and pharmacological approaches to correct lipid metabolism. A number of these approaches have contributed to reducing the risk of CVD, which has led to the widespread introduction of these drugs into practice (Table 3).
Table 3. Main classes of drugs used to treat lipid metabolism disorders.

Pharmaceutical group	LDL	Triglycerides	HDL