Fat metabolism

The metabolism of fats includes the metabolism of neutral fats, phosphatides, glycolipids, cholesterol and steroids. Such a large number of components included in the concept of fats makes it extremely difficult to describe the features of their metabolism. However, their general physicochemical property - low solubility in water and good solubility in organic solvents - allows us to immediately emphasize that the transport of these substances in aqueous solutions is possible only in the form of complexes with protein or bile acid salts or in the form of soaps.

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The Importance of Fat for the Body

In recent years, the view on the importance of fats in human life has changed significantly. It turned out that fats in the human body are quickly renewed. Thus, half of all fat in an adult is renewed within 5-9 days, fat in adipose tissue - 6 days, and in the liver - every 3 days. After the high rate of renewal of fat depots in the body was established, fats are given a large role in energy metabolism. The importance of fats in the construction of the most important structures of the body (for example, the membrane of nerve tissue cells), in the synthesis of adrenal hormones, in protecting the body from excessive heat loss, in the transportation of fat-soluble vitamins has long been well known.

Body fat corresponds to two chemical and histological categories.

A - "essential" fat, which includes lipids that are part of the cells. They have a certain lipid spectrum, and their amount is 2-5% of the body weight without fat. "Essential" fat is retained in the body even during prolonged starvation.

B - "non-essential" fat (reserve, excess), located in the subcutaneous tissue, in the yellow bone marrow and abdominal cavity - in the fatty tissue located near the kidneys, ovaries, in the mesentery and omentum. The amount of "non-essential" fat is not constant: it is either accumulated or used depending on energy expenditure and the nature of nutrition. Studies of the body composition of fetuses of different ages have shown that fat accumulation in their bodies occurs mainly in the last months of pregnancy - after 25 weeks of gestation and during the first-second year of life. Fat accumulation during this period is more intense than protein accumulation.

Dynamics of protein and fat content in the body weight structure of the fetus and child

Body weight of the fetus or child, g	Protein, %	Fat, %	Protein, g	Fat, g
1500	11.6	3.5	174	52.5
2500	12.4	7.6	310	190
3500	12.0	16.2	420	567
7000	11.8	26.0	826	1820

Such intensity of accumulation of adipose tissue in the period of the most critical growth and differentiation testifies to the leading use of fat as a plastic material, but not as an energy reserve. This can be illustrated by data on the accumulation of the most essential plastic component of fat - polyunsaturated long-chain fatty acids of classes ω3 and ω6, which are included in brain structures and determine the functional properties of the brain and the visual apparatus.

Accumulation of ω-fatty acids in fetal and child brain tissue

Fatty acids	Before birth, mg/week	After birth, mg/week
Total ω6	31	78
18:2	1	2
20:4	19	45
Total ω3	15	4
18:3	181	149

The lowest amount of fat is observed in children in the prepubertal period (6-9 years). With the onset of puberty, an increase in fat reserves is again observed, and at this time there are already pronounced differences depending on gender.

Along with the increase in fat reserves, the glycogen content increases. Thus, energy reserves are accumulated for use in the initial period of postnatal development.

While the passage of glucose through the placenta and its accumulation as glycogen are well known, most researchers believe that fats are synthesized only in the fetus. Only the simplest acetate molecules, which can be the starting products for fat synthesis, pass through the placenta. This is evidenced by the different fat content in the blood of the mother and child at the time of birth. For example, the cholesterol content in the mother's blood averages 7.93 mmol/l (3050 mg/l), in retroplacental blood - 6.89 (2650 mg/l), in umbilical cord blood - 6.76 (2600 mg/l), and in the child's blood - only 2.86 mmol/l (1100 mg/l), i.e. almost 3 times lower than in the mother's blood. The intestinal digestion and absorption systems of fats are formed comparatively early. They find their first application already at the beginning of the ingestion of amniotic fluid - i.e. amniotrophic nutrition.

Timing of the development of gastrointestinal tract functions (timing of detection and severity as a percentage of the same function in adults)

Digestion of fat	First identification of an enzyme or function, week	Functional expression as a percentage of an adult
Sublingual lipase	30	More than 100
Pancreatic lipase	20	5-10
Pancreatic colipase	Unknown	12
Bile acids	22	50
Medium chain triglyceride absorption	Unknown	100
Absorption of long-chain triglycerides	Unknown	90

Features of fat metabolism depending on age

Fat synthesis occurs mainly in the cytoplasm of cells along the path that is the reverse of the Knoop-Linen fat breakdown cycle. Fatty acid synthesis requires the presence of hydrogenated nicotinamide enzymes (HAOP), especially HAOP H2. Since the main source of HAOP H2 is the pentose cycle of carbohydrate breakdown, the intensity of fatty acid formation will depend on the intensity of the pentose cycle of carbohydrate breakdown. This emphasizes the close connection between fat and carbohydrate metabolism. There is a figurative expression: "fats burn in the flame of carbohydrates."

The amount of "non-essential" fat is affected by the nature of feeding children in the first year of life and their nutrition in subsequent years. With breastfeeding, the body weight of children and their fat content are somewhat less than with artificial feeding. At the same time, breast milk causes a transient increase in cholesterol content in the first month of life, which serves as a stimulus for earlier synthesis of lipoprotein lipase. It is believed that this is one of the factors that inhibit the development of atheromatosis in subsequent years. Excessive nutrition of young children stimulates the formation of cells in adipose tissue, which later manifests itself as a tendency to obesity.

There are also differences in the chemical composition of triglycerides in the adipose tissue of children and adults. Thus, the fat of newborns contains relatively less oleic acid (69%) compared to adults (90%) and, conversely, more palmitic acid (in children - 29%, in adults - 8%), which explains the higher melting point of fats (in children - 43 ° C, in adults - 17.5 ° C). This should be taken into account when organizing care for children in the first year of life and when prescribing them drugs for parenteral use.

After birth, the need for energy to ensure all vital functions increases sharply. At the same time, the supply of nutrients from the mother's body ceases, and the supply of energy with food in the first hours and days of life is insufficient, not even covering the needs of basic metabolism. Since the child's body has enough carbohydrate reserves for a relatively short period, the newborn is forced to immediately use fat reserves, which is clearly manifested by an increase in the concentration of non-esterified fatty acids (NEFA) in the blood with a simultaneous decrease in the concentration of glucose. NEFA are a transport form of fat.

Simultaneously with the increase in the content of NEFA in the blood of newborns, the concentration of ketones begins to increase after 12-24 hours. There is a direct dependence of the level of NEFA, glycerol, ketones on the energy value of food. If a child is given a sufficient amount of glucose immediately after birth, the content of NEFA, glycerol, ketones will be very low. Thus, the newborn covers its energy costs primarily through carbohydrate metabolism. As the amount of milk that the child receives increases, its energy value increases to 467.4 kJ (40 kcal / kg), which covers at least the basic metabolism, the concentration of NEFA falls. Studies have shown that the increase in the content of NEFA, glycerol and the appearance of ketones are associated with the mobilization of these substances from adipose tissue, and do not represent a simple increase due to incoming food. With regard to other components of fats - lipids, cholesterol, phospholipids, lipoproteins - it has been established that their concentration in the blood of the umbilical vessels of newborns is very low, but after 1-2 weeks it increases. This increase in the concentration of non-transport fractions of fat is closely related to their intake with food. This is due to the fact that the food of a newborn - breast milk - has a high fat content. Studies conducted on premature babies have yielded similar results. It seems that after the birth of a premature baby, the duration of intrauterine development is less important than the time elapsed after birth. After the start of breastfeeding, fats taken with food are subject to breakdown and resorption under the influence of lipolytic enzymes of the gastrointestinal tract and bile acids in the small intestine. Fatty acids, soaps, glycerol, mono-, di- and even triglycerides are resorbed in the mucous membrane of the middle and lower sections of the small intestine. Resorption can occur both by pinocytosis of small fat droplets by intestinal mucosal cells (chylomicron size less than 0.5 μm) and in the form of formation of water-soluble complexes with bile salts and acids, cholesterol esters. At present, it has been proven that fats with a short carbon chain of fatty acids (C 12) are absorbed directly into the blood of the v. portae system. Fats with a longer carbon chain of fatty acids enter the lymph and through the common thoracic duct flow into the circulating blood. Due to the insolubility of fats in the blood, their transport in the body requires certain forms. First of all, lipoproteins are formed. The transformation of chylomicrons into lipoproteins occurs under the influence of the enzyme lipoprotein lipase ("clarifying factor"), the cofactor of which is heparin. Under the influence of lipoprotein lipase, free fatty acids are split from triglycerides, which are bound by albumins and thus easily absorbed. It is known that α-lipoproteins contain 2/3 of phospholipids and about 1/4 of cholesterol in blood plasma, β-lipoproteins - 3/4 of cholesterol and 1/3 of phospholipids.In newborns, the amount of α-lipoproteins is significantly higher, while β-lipoproteins are few. Only by 4 months does the ratio of α- and β-fractions of lipoproteins approach the normal values for an adult (α-fractions of lipoproteins - 20-25%, p-fractions of lipoproteins - 75-80%). This has a certain significance for the transport of fat fractions.

Fat exchange is constantly taking place between fat depots, liver and tissues. In the first days of a newborn's life, the content of esterified fatty acids (EFAs) does not increase, while the concentration of NEFAs increases significantly. Consequently, in the first hours and days of life, re-esterification of fatty acids in the intestinal wall is reduced, which is also confirmed by the free fatty acid load.

Steatorrhea is often observed in children of the first days and weeks of life. Thus, the excretion of total lipids with feces in children under 3 months is on average about 3 g / day, then at the age of 3-12 months it decreases to 1 g / day. At the same time, the amount of free fatty acids in feces also decreases, which reflects better absorption of fat in the intestine. Thus, the digestion and absorption of fats in the gastrointestinal tract at this time is still imperfect, since the intestinal mucosa and pancreas undergo a process of functional maturation after birth. In premature infants, lipase activity is only 60-70% of the activity found in children over 1 year old, while in full-term newborns it is higher - about 85%. In infants, lipase activity is almost 90%.

However, lipase activity alone does not determine fat absorption. Another important component that promotes fat absorption is bile acids, which not only activate lipolytic enzymes, but also directly affect fat absorption. Bile acid secretion has age-related characteristics. For example, in premature infants, the secretion of bile acids by the liver is only 15% of the amount that is formed during the period of full development of its function in children aged 2 years. In full-term infants, this value increases to 40%, and in children of the first year of life it is 70%. This circumstance is very important from the point of view of nutrition, since half of the children's energy needs are covered by fat. Since we are talking about breast milk, digestion and absorption are quite complete. In full-term infants, fat absorption from breast milk occurs at 90-95%, in premature infants it is slightly less - at 85%. With artificial feeding, these values decrease by 15-20%. It has been established that unsaturated fatty acids are absorbed better than saturated ones.

Human tissues can break down triglycerides to glycerol and fatty acids and synthesize them back. Triglyceride breakdown occurs under the influence of tissue lipases, passing through intermediate stages of di- and monoglycerides. Glycerol is phosphorylated and included in the glycolytic chain. Fatty acids undergo oxidative processes localized in the mitochondria of cells and are exchanged in the Knoop-Linen cycle, the essence of which is that with each turn of the cycle, one molecule of acetyl coenzyme A is formed and the fatty acid chain is reduced by two carbon atoms. However, despite the large increase in energy during the breakdown of fats, the body prefers to use carbohydrates as an energy source, since the possibilities of autocatalytic regulation of energy growth in the Krebs cycle from the side of carbohydrate metabolism pathways are greater than in the metabolism of fats.

During fatty acid catabolism, intermediate products are formed - ketones (β-hydroxybutyric acid, acetoacetic acid and acetone). Their quantity has a certain value, since carbohydrates in food and some amino acids have anti-ketone properties. In simplified terms, the ketogenicity of the diet can be expressed by the following formula: (Fats + 40% proteins) / (Carbohydrates + 60% proteins).

If this ratio is greater than 2, then the diet has ketonic properties.

It should be borne in mind that regardless of the type of food, there are age-related features that determine the tendency to ketosis. Children aged 2 to 10 years are especially predisposed to it. On the contrary, newborns and children of the first year of life are more resistant to ketosis. It is possible that the physiological "maturation" of the activity of enzymes involved in ketogenesis occurs slowly. Ketones are formed mainly in the liver. When ketones accumulate, acetonemic vomiting syndrome occurs. Vomiting occurs suddenly and can continue for several days and even weeks. When examining patients, an apple odor from the mouth (acetone) is detected, and acetone is detected in the urine. At the same time, the sugar content in the blood is within normal limits. Ketoacidosis is also characteristic of diabetes mellitus, in which hyperglycemia and glucosuria are detected.

Unlike adults, children have age-related characteristics of their blood lipid profile.

Age-related features of fat content and its fractions in children

Indicator	Newborn			G infant 1-12 months	Children from 2
	1 hour	24 h	6-10 days		Up to 14 years old
Total lipids, g/l	2.0	2.21	4.7	5.0	6.2
Triglycerides, mmol/l	0.2	0.2	0.6	0.39	0.93
Total cholesterol, mmol/l	1.3	-	2.6	3.38	5.12
Effectively bound cholesterol, % of total	35.0	50.0	60.0	65.0	70.0
NEFA, mmol/l	2,2	2.0	1,2	0.8	0.45
Phospholipids, mmol/l	0.65	0.65	1.04	1.6	2.26
Lecithin, g/l	0.54	-	0.80	1.25	1.5
Kefalin, g/l	0.08	-	-	0.08	0.085

As can be seen from the table, the content of total lipids in the blood increases with age: during the first year of life alone, it increases almost 3 times. Newborns have a relatively high content (as a percentage of the total fat) of neutral lipids. During the first year of life, the content of lecithin increases significantly with relative stability of cephalin and lysolecithin.

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Fat metabolism disorder

Disturbances in fat metabolism can occur at various stages of its metabolism. Although rare, Sheldon-Reye syndrome is observed - fat malabsorption caused by the absence of pancreatic lipase. Clinically, this is manifested by a celiac-like syndrome with significant steatorrhea. As a result, the body weight of patients increases slowly.

Changes in erythrocytes are also detected due to disruption of the structure of their membrane and stroma. A similar condition occurs after surgical interventions on the intestine, in which significant sections of it are resected.

Impaired digestion and absorption of fat is also observed with hypersecretion of hydrochloric acid, which inactivates pancreatic lipase (Zollinger-Ellison syndrome).

Among the diseases based on the disorder of fat transport, abetalipoproteinemia is known - the absence of β-lipoproteins. The clinical picture of this disease is similar to that of celiac disease (diarrhea, hypotrophy, etc.). In the blood - low fat content (serum is transparent). However, various hyperlipoproteinemias are observed more often. According to the WHO classification, five types are distinguished: I - hyperchylomicronemia; II - hyper-β-lipoproteinemia; III - hyper-β-hyperpre-β-lipoproteinemia; IV - hyperpre-β-lipoproteinemia; V - hyperpre-β-lipoproteinemia and chylomicronemia.

Main types of hyperlipidemia

Indicators	Type of hyperlipidemia
	I	IIA	IIv	III	IV	V
Triglycerides	Increased		Increased		Increased	↑
Chylomicrons						↑
Total cholesterol		Increased	Increased
Lipoprotein lipase	Reduced
Lipoproteins		Increased	Increased	Increased
Very low density lipoproteins			Increased		Increased	↑

Depending on the changes in blood serum in hyperlipidemia and the content of fat fractions, they can be distinguished by transparency.

Type I is based on a deficiency of lipoprotein lipase, the blood serum contains a large number of chylomicrons, as a result of which it is cloudy. Xanthomas are often found. Patients often suffer from pancreatitis, accompanied by attacks of acute abdominal pain, and retinopathy is also found.

Type II is characterized by an increase in the blood content of β-lipoproteins of low density with a sharp increase in the level of cholesterol and normal or slightly increased content of triglycerides. Clinically, xanthomas on the palms, buttocks, periorbital, etc. are often detected. Arteriosclerosis develops early. Some authors distinguish two subtypes: IIA and IIB.

Type III - an increase in the so-called floating β-lipoproteins, high cholesterol, moderate increase in triglyceride concentration. Xanthomas are often found.

Type IV - increased pre-β-lipoprotein levels with increased triglycerides, normal or slightly elevated cholesterol levels; chylomicronemia is absent.

Type V is characterized by an increase in low-density lipoproteins with a decrease in the clearance of plasma from dietary fats. The disease is clinically manifested by abdominal pain, chronic recurrent pancreatitis, and hepatomegaly. This type is rare in children.

Hyperlipoproteinemias are more often genetically determined diseases. They are classified as lipid transport disorders, and the list of these diseases is becoming more and more complete.

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Diseases of the lipid transport system

• Family:
  • hypercholesterolemia;
  • disorders of apo-B-100 synthesis;
  • combined hyperlipidemia;
  • hyperapolipo-β-lipoproteinemia;
  • dys-β-lipoproteinemia;
  • phytosterolemia;
  • hypertriglyceridemia;
  • hyperchylomicronemia;
  • type 5 hyperlipoproteinemia;
  • hyper-α-lipoproteinemia type Tangier disease;
  • lecithin/cholesterol acyltransferase deficiency;
  • an-α-lipoproteinemia.
• Abetalipoproteinemia.
• Hypobetalipoproteinemia.

However, these conditions often develop secondarily to various diseases (lupus erythematosus, pancreatitis, diabetes mellitus, hypothyroidism, nephritis, cholestatic jaundice, etc.). They lead to early vascular damage - arteriosclerosis, early formation of ischemic heart disease, the risk of developing hemorrhages in the brain. Over the past decades, attention has been constantly growing to the childhood origins of chronic cardiovascular diseases in adulthood. It has been described that even in young people, the presence of lipid transport disorders can lead to the formation of atherosclerotic changes in the vessels. Among the first researchers of this problem in Russia were V. D. Tsinzerling and M. S. Maslov.

Along with this, intracellular lipoidoses are also known, among which Niemann-Pick disease and Gaucher disease are most common in children. In Niemann-Pick disease, sphingomyelin is deposited in the cells of the reticuloendothelial system and in the bone marrow, and in Gaucher disease, hexosecerebrosides. One of the main clinical manifestations of these diseases is splenomegaly.

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