Pathological factors of obesity: mechanisms of fat synthesis, digestion, absorption and mobilization

Pathological factors of obesity

30. How is fat synthesized in obesity?

Human adipose tissue is composed of fat cells, which are composed of triglycerides.

Fats are synthesized from fatty acids (stearic acid, palmitic acid, oleic acid) and glycerol. Dietary lipids can be modified and stored directly. Even the remaining sugars and proteins (mainly sugars) can be converted into triglycerides and stored in fat stores.

Fatty acids are mainly provided by oils or high-fat foods, while glycerol is provided by glucose in the blood. Of course, initially, they are still supplied by carbohydrates in food.

Blood glucose plays a leading role in regulating lipid metabolism. When there is a sufficient supply of blood glucose, it enters fat cells under the action of insulin. Except for a small amount that is synthesized into glycogen, most of it is converted into fat or oxidized and decomposed to provide energy.

Glucose plays three roles in the synthesis of triglycerides in adipocytes: first, it provides α-glycerol phosphate through glycolysis; second, it provides acetyl-CoA, the active raw material for fatty acid synthesis, through pyruvate oxidation and decarboxylation; and third, it provides NADPH₂, the reducing agent for fatty acid synthesis, through the fructose phosphate pathway.

31. How is fat digested and absorbed in the human body?

The vast majority of fats in food are long-chain fats, with only foods like cheese and cocoa containing a significant amount of short-chain and medium-chain fats.

Because saliva does not contain the enzymes that digest fat, fat cannot be digested in the mouth.

There is only a small amount of lipase in gastric juice, but because the optimal pH of this enzyme is 6.5 to 7.0, which is far from the pH of gastric juice (around 5), only infants or adults with low gastric acidity, or fully emulsified fats (such as milk and egg yolks) can be digested in small amounts in the stomach.

Fat digestion mainly occurs in the small intestine. Food passes through the duodenum and produces gastrointestinal hormones, which stimulate the secretion of pancreatic juice and bile.

Pancreatic juice contains pancreatic lipase, which can partially hydrolyze fats into glycerol and free fatty acids, and most of them are hydrolyzed into β-glycerol monoesters, which are then absorbed by the small intestine.

Bile salts in bile can emulsify fats, which facilitates the hydrolysis of fats by pancreatic fatty acids and the absorption of fat digestion products.

Bile salts, monoglycerides, fatty acids, and cholesterol form mixed microparticles of digestive products. These products pass through the lipoprotein membrane of the non-flowing aqueous layer on the surface of the small intestinal villi and enter the mucosal cells. The absorbed fatty acids and monoglycerides are transported to the endoplasmic reticulum by fatty acid-binding proteins (FABP) within the mucosal cells, and then synthesized into chylomicrons by the smooth endoplasmic reticulum.

Chylomicrons are 98% fat; small amounts of phospholipids, cholesterol, and apolipoproteins.

Chylomicrons are then secreted through the Golgi complex and the serous membrane of mucosal cells, entering the central lacteals, lymphatic vessels, and finally the bloodstream.

If the process of digesting and absorbing fat is slowed down or reduced, it is possible to lose weight.

32. What is the mechanism of fat mobilization in the body?

Fat in the body's fat stores is often partially hydrolyzed into glycerol and fatty acids by lipases and released; this process is called fat mobilization.

Lipase regulation is influenced by a variety of hormones, and these are called hormone-sensitive lipases.

Glucagon, adrenocorticotropic hormone (ACTH), and thyroid-stimulating hormone (TSH) can all activate adenylate cyclase on the adipocyte membrane, increase intracellular C-AMP concentration, activate hormone-sensitive lipase, and accelerate fat mobilization.

Thyroid hormones can increase the sensitivity of receptors on adipocyte membranes to catecholamines and glucagon, thus synergistically promoting fat mobilization.

Cortisol inhibits glucose uptake and utilization by adipose tissue, reduces fatty acid reesterification, inhibits phosphodiesterase activity, reduces C-AMP breakdown, and accelerates fat mobilization.

Growth hormone promotes the synthesis of lipase and enhances fat mobilization.

Prostaglandins (PGs) can inhibit adenylate cyclase, reduce the production of C-AMP, and decrease fat mobilization.

In addition to the hormones mentioned above, factors affecting fat mobilization include sympathetic nerve excitation and elevated catecholamine levels, which can also increase fat mobilization.

Theophylline can inhibit phosphodiesterase, increase C-AMP, and promote fat mobilization.

In normal individuals, the hormones that induce fat mobilization are in a relatively balanced state, so the accumulation and mobilization of fat are also in a balanced state. If this balance is disrupted, it will cause fat metabolism disorders, leading to obesity or emaciation and changes in blood lipid levels.