Fat exchange

The exchange of fats involves the exchange of neutral fats, phosphatides, glycolipids, cholesterol and steroids. Such a large number of components, which are part of 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 the protein or bile salts or in the form of soaps.

[1], [2], [3], [4], [5], [6]

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 quickly updated. So, half of all fat in an adult is renewed for 5-9 days, adipose tissue fat - 6 days, and in the liver - every 3 days. After the high rate of renewal of fat stores of the body was established, fats are given a big role in energy metabolism. The importance of fats in building the most important structures of the body (for example, the cladding of cells of the nervous tissue), in the synthesis of adrenal hormones, in protecting the body from excessive heat transfer, in transporting fat-soluble vitamins has long been well known.

Body fat corresponds to two chemical and histological categories.

A - "essential" fat, to which belong the lipids that make up the cells. They have a certain lipid spectrum, and their amount is 2-5% of body weight without fat. "Essential" fat is stored in the body and with prolonged starvation.

B - "insignificant" fat (spare, redundant), located in the subcutaneous fat, in the yellow bone marrow and abdominal cavity - in adipose tissue located near the kidneys, ovaries, in the mesentery and the omentum. The amount of "insignificant" fat is unstable: it either accumulates, or is used depending on the energy expenditure and the nature of the food. Studies of the body composition of fetuses of different ages have shown that the accumulation of fat in their bodies occurs mainly in the last months of pregnancy - after 25 weeks of gestation and during the first-second year of life. The accumulation of fat during this period is more intense than the accumulation of protein.

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

Fetal or child body mass, 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

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

Accumulation of ω-fatty acids in the brain tissue of the fetus and the baby

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

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

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

If the transition of glucose through the placenta and its accumulation in the form of glycogen is well known, then, according to most researchers, fats are synthesized only in the fetus. Only the simplest molecules of acetate pass through the placenta, which can be the starting products for fat synthesis. 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 retrocolar blood - 6.89 (2650 mg / l), in the cord blood - 6.76 (2600 mg / l), and in the blood of the child - only 2.86 mmol / l (1100 mg / l), ie, almost 3 times lower than in the mother's blood. Relatively early formed systems of intestinal digestion and absorption of fats. They find their first application already at the beginning of ingestion of amniotic fluid - that is, amniotropic nutrition.

The timing of the formation of functions of the gastrointestinal tract (terms of detection and severity as a percentage of a similar function in adults)

Digestion of fat	The first detection of an enzyme or function, weeks	Expression of function as a percentage of an adult
Sublingual lipase	Thirty	More than 100
Pancreatic lipase	20	5-10
Colicase pancreatic	Unknown	12
Bile acids	22	50
Assimilation of medium chain triglycerides	Unknown	100
Assimilation of long chain triglycerides	Unknown	90

Features of fat metabolism depending on age

The synthesis of fat occurs predominantly in the cytoplasm of cells along the path opposite to the decay of fat by Knoopu-Lienen. The synthesis of fatty acids requires the presence of hydrogenated nicotinamide enzymes (NAOPs), especially NAOP H2. Since the main source of NAOP H2 is the pentose carbohydrate decay cycle, the rate of formation of fatty acids will depend on the intensity of the pentose carbohydrate cleavage cycle. This emphasizes the close relationship of the metabolism of fats and carbohydrates. There is a figurative expression: "fats burn in the flame of carbohydrates."

The size of "insignificant" fat affects the nature of feeding of children in the first year of life and feeding them in subsequent years. When breastfeeding the body weight of children and the fat content of them is somewhat less than with artificial. At the same time, breast milk causes a transient increase in cholesterol in the first month of life, which serves as a stimulus to an earlier synthesis of lipoprotein lipase. It is believed that this is one of the factors hindering the development of atheromatosis in subsequent years. Excessive nutrition of young children stimulates the formation of adipose tissue cells, which in the future manifests a tendency to obesity.

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

After birth, there is a sharp increase in the need for energy to ensure all life functions. At the same time, the supply of nutrients from the mother's body stops, and the delivery of energy with food in the first hours and days of life is insufficient, not even covering the need for basic metabolism. Since the child's carbohydrate reserves are enough for a relatively short period in the child's body, the newborn must immediately use fat reserves, which is clearly manifested by a rise in the concentration of non-esterified fatty acids in the blood while lowering the glucose concentration. NEFIC are the transport form of fat.

Simultaneously with the increase in the content of NEFLC in the blood of newborns, the concentration of ketones begins to increase after 12-24 h. There is a direct correlation between the level of NEFLC, glycerol, and ketones on the energy value of food. If immediately after birth, the child is given enough glucose, then the content of NEFLC, glycerin, ketones will be very low. Thus, the newborn covers its energy costs primarily through the exchange of carbohydrates. With the increase in the amount of milk that the child receives, increasing its energy value to 467.4 kJ (40 kcal / kg), which covers at least the main metabolism, the concentration of NLCL falls. Studies have shown that an increase in the content of NEFLC, glycerin 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 ingestion. Concerning other components of fats - lipids, cholesterol, phospholipids, lipoproteins - it is established that their concentration in the blood of the umbilical vessels in newborns is very low, but after 1-2 weeks it increases. This increase in the concentration of non-transportable fractions of fat is closely related to their intake from food. This is due to the fact that in the food of the newborn - breast milk - a high fat content. Studies conducted in preterm infants 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 that has passed since birth. After the beginning of breastfeeding, the fats taken from food are subjected to splitting and resorption under the influence of lipolytic enzymes of the gastrointestinal tract and bile acids in the small intestine. Fatty acids, soaps, glycerin, mono-, di- and even triglycerides are resorbed in the mucosa of the middle and lower divisions of the small intestine. Resorption can occur both by pinocytosis of small fat droplets by cells of the intestinal mucosa (chylomicron size less than 0.5 microns), and in the form of water-soluble complexes with bile salts and acids, cholesterol esters. Now it is proved that fats with a short carbon chain of fatty acids (C 12) are absorbed directly into the blood of the system v. Portae. Fats with a longer carbon chain of fatty acids enter the lymph and through the common chest duct are poured into the circulating blood. Because of 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 lipoprotein lipase enzyme ("clarifying factor"), the cofactor of which is heparin. Under the influence of lipoprotein lipase, free fatty acids are cleaved from triglycerides, which are bound by albumins and thus easily digested. It is known that α-lipoproteins contain 2/3 phospholipids and about 1/4 of the blood plasma cholesterol, β-lipoproteins - 3/4 cholesterol and 1/3 phospholipids. In newborns, the amount of α-lipoproteins is much larger, whereas β-lipoproteins are few. Only at 4 months the ratio of α- and β-fractions of lipoproteins approaches normal for adult values (α-fractions of lipoproteins - 20-25%, p-fractions of lipoproteins - 75-80%). This has a certain value for the transport of fat fractions.

Between the fat depots, liver and tissues, there is a constant exchange of fats. In the first days of a newborn's life, the content of esterified fatty acids (EFA) does not increase, while the concentration of NEFIC is significantly increased. Consequently, in the first hours and days of life, the re-esterification of fatty acids in the intestinal wall is reduced, which is also confirmed when loaded with free fatty acids.

In children of the first days and weeks of life, steatorrhea is often observed. So, the allocation of total lipids with feces in children up to 3 months is an average of 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 decreases in feces, which reflects the best 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 the pancreas undergo a functional maturation process after birth. In premature newborns, lipase activity is only 60-70% of the activity found in children older than 1 year, while in full-term newborns it is higher - about 85%. In infants, lipase activity is almost 90%.

However, only the activity of lipase does not yet determine the absorption of fat. Another important component contributing to the absorption of fats is bile acids, which not only activate lipolytic enzymes, but also directly affect the absorption of fat. Secretion of bile acids has age characteristics. For example, in preterm infants the release 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 2 years old. In term infants, this value rises 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 the children's energy needs are covered by fat. As far as breast milk is concerned, digestion and absorption are very complete. At full-term children, the absorption of fats from breast milk occurs by 90-95%, in preterm babies it is somewhat less - by 85%. With artificial feeding, these values are reduced by 15-20%. It was found that unsaturated fatty acids are absorbed better than saturated ones.

Human tissues can split triglycerides to glycerol and fatty acids and synthesize them back. The cleavage of triglycerides occurs under the influence of tissue lipases, passing through the intermediate stages of di- and monoglycerol. Glycerin is phosphorylated and incorporated into the glycolytic chain. Fatty acids are subjected to oxidative processes localized in the mitochondria of cells and are exchanged in the Knoop-Linen cycle, the essence of which is that at each revolution of the cycle one molecule of acetylcoenzyme A is formed and the chain of fatty acid is reduced by two carbon atoms. However, despite the large increase in energy in the breakdown of fats, the body prefers to use carbohydrates as an energy source, since the possibilities for autocatalytic regulation of energy gain in the Krebs cycle from the carbohydrate metabolism pathway are greater than in the case of fat metabolism.

With the catabolism of fatty acids, intermediate products - ketones (β-hydroxybutyric acid, acetoacetic acid and acetone) form. Their quantity has a certain value, since carbohydrates of food and part of amino acids possess anti-ketone properties. Simplified ketogenicity of the diet can be expressed by the following formula: (Fats + 40% protein) / (carbohydrates + 60% protein).

If this ratio exceeds 2, then the diet has ketone properties.

It should be borne in mind that, regardless of the type of food, there are age characteristics that determine the propensity to ketosis. Children between the ages of 2 to 10 years are particularly prone to it. Conversely, 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 is slow. The formation of ketones is mainly carried out in the liver. With the accumulation of ketones, acetone-induced vomiting arises. Vomiting occurs suddenly and can last for several days and even weeks. When examining patients, apple odor from the mouth (acetone) is detected, and in the urine acetone is determined. In the blood, the sugar content is within normal limits. Ketoacidosis is also characteristic of diabetes mellitus, in which hyperglycemia and glucosuria are found.

Unlike adults, children have age-specific features of the blood lipidogram.

Age features of the content of fat and its fractions in children

Index	Newborn			Ore child 1-12 months	Children from 2
	1 h	24 h	6-10 days		Under 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
Cholesterol total, mmol / l	1.3	-	2.6	3.38	5.12
Effective cholesterol,% of total	35.0	50.0	60.0	65.0	70.0
NLELC, 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 rises with age: only during the first year of life it increases almost 3-fold. Newborns have a relatively high content (as a percentage of total fat) of neutral lipids. In the first year of life, the content of lecithin increases significantly with the relative stability of kefalin and lysolecithin.

[7], [8], [9], [10], [11], [12]

Disturbance of fat metabolism

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

There is also a change in erythrocytes due to a violation of the structure of their shell and stroma. A similar condition occurs after surgery on the intestine, in which its significant areas are resected.

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

Of the diseases, which are based on a violation 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 - a low fat content (the serum is transparent). However, more often there are various hyperlipoproteinemia. According to WHO classification, five types are distinguished: I - hyperchylomicronemia; II - hyper-β-lipoproteinemia; III - hyper-β-hyperpregn-β-lipoproteinemia; IV - Hyperpre-β-lipoproteinemia; V - hyperprep-β-lipoproteinemia and chylomicronemia.

The main types of hyperlipidemia

Indicators	Type of hyperlipidemia
	I	IIA	IIb	III	IV	V
Triglycerides	Increased		Increased		Increased	↑
Chylomicrons						↑
Cholesterol total		Enhanced	Enhanced
Lipoprotein-lipase	Decreased
Lipoproteins		Increased	Increased	Increased
Very low density lipoproteins			Increased		Increased	↑

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

Type I is based on a deficiency of lipoprotein lipase, the serum contains a large number of chylomicrons, as a result of which it is turbid. Often there are xanthomas. Patients often suffer from pancreatitis, accompanied by attacks of acute pain in the abdomen, and retinopathy is also found.

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

III type - increase of so-called flotation β-lipoproteins, high cholesterol, moderate increase in triglyceride concentration. Often there are xanthomas.

IV type - an increase in the content of pre-β-lipoproteins with increasing triglycerides, normal or slightly elevated cholesterol; chylomicronemia is absent.

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

Hyperlipoproteinemia is often a genetically determined disease. They are classified as a violation of lipid transfer, and the list of these diseases is becoming more complete.

[13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24]

Diseases of the lipid transport system

• Family:
  • hypercholesterolemia;
  • violation of the synthesis of apo-B-100;
  • combined hyperlipidemia;
  • hyperapo-β-lipoproteinemia;
  • dis-β-lipoproteinemia;
  • phytosterolia;
  • hypertriglyceridemia;
  • hyperhylomicronemia;
  • type 5-hyperlipoproteinemia;
  • hyper-α-lipoproteinemia such as Tangier disease;
  • insufficiency of lecithin / cholesterol acyltransferase;
  • an-α-lipoproteinemia.
• Abetalipoproteinemia.
• Hypobetalipoproteinemia.

However, often these conditions develop again for various diseases (lupus erythematosus, pancreatitis, diabetes mellitus, hypothyroidism, nephritis, cholestatic jaundice, etc.). They lead to early vascular damage - arteriosclerosis, early formation of coronary heart disease, the danger of developing cerebral hemorrhages. During the last decades, the attention to the children's sources of chronic cardiovascular diseases of the adult period of life is constantly growing. It is described that in young people the presence of violations of lipid transport can lead to the formation of atherosclerotic changes in the vessels. One of the first researchers of this problem in Russia was VD Zinzerling and MS Maslov.

In addition, intracellular lipoids are known, among which the children of the Niemen-Pick disease and Gaucher disease are most often found in children. With Niman-Pick disease, deposits in the cells of the reticuloendothelial system, in the bone marrow of sphingomyelin, and in Gaucher's disease - hexosocerebrosides are observed. One of the main clinical manifestations of these diseases is splenomegaly.

[25], [26], [27], [28]