Lipid adipose tissue release

Niacin (vitamin B3) has broad applications in the treatment of lipid disorders when used at higher doses than those used as a nutritional supplement. Niacin inhibits fatty acid release from adipose tissue and inhibits fatty acid and triglyceride production in liver cells. This results in an increased intracellular degradation of apolipoprotein B, and in turn, a reduction in the number of VLDL particles secreted (Fig. 9-4). The lower VLDL levels and the lower triglyceride content in these particles leads to an overall reduction in LDL cholesterol as well as a decrease in the number of small, dense LDL particles. Niacin also reduces the uptake of HDL-apolipoprotein A1 particles and increases uptake of cholesterol esters by the liver, thus improving the efficiency of reverse cholesterol transport between HDL particles and vascular tissue (Fig. 9-4). Niacin is indicated for patients with elevated triglycerides, low HDL cholesterol, and elevated LDL cholesterol.3... 

Intravenous lipid emulsion particles are hydrolyzed in the bloodstream by the enzyme lipoprotein lipase to release free fatty acids and glycerol. Free fatty acids then are be taken up into adipose tissue for storage (triglycerides), oxidized to energy in various tissues (e.g., skeletal muscle), or recycled in the liver to make lipoproteins. 

As is known, hydrolysis of intracellular lipids does not lead to a storage of glycerol and fatty acids. This indicates that the hydrolysis rate for the lipids is balanced against the rate of their intracellular oxidation. In the adipose tissue, glycerol and fatty acids as produced by triacylglycejride hydrolysis are not subject to oxidation and are released into the blood to be supplied to other organs. 

The major types of adipose tissue are (1) white adipose tissue, which manufactures, stores, and releases lipid and (2) brown adipose tissue, which dissipates energy via uncoupled mitochondrial respiration. Obesity research includes evaluation of the activity of adrenergic receptors and their effect on adipose tissue with respect to energy storage and expenditure or thermogenesis. 

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

FIGURE 17-1 Processing of dietary lipids in vertebrates Digestion and absorption of dietary lipids occur in the small intestine, and the fatty acids released from triacylglycerols are packaged and delivered to muscle and adipose tissues. The eight steps are discussed in the text. 

When the diet contains more fatty acids than are needed immediately as fuel, they are converted to triacylglycerols in the liver and packaged with specific apolipoproteins into very-low-density lipoprotein (VLDL). Excess carbohydrate in the diet can also be converted to triacylglycerols in the liver and exported as VLDLs (Fig. 21-40a). In addition to triacylglycerols, VLDLs contain some cholesterol and cholesteryl esters, as well as apoB-100, apoC-I, apoC-II, apoC-III, and apo-E (Table 21-3). These lipoproteins are transported in the blood from the liver to muscle and adipose tissue, where activation of lipoprotein lipase by apoC-II causes the release of free fatty acids from the VLDL triacylglycerols. Adipocytes take up these fatty acids, reconvert them to triacylglycerols, and store the products in intracellular lipid droplets myocytes, in contrast, primarily oxidize the fatty acids to supply energy. Most VLDL remnants are removed from the circulation by hepatocytes. The uptake, like that for chylomicrons, is... 

The amount of leptin released by adipose tissue depends on both the number and the size of adipocytes. When weight loss decreases the mass of lipid tissue, leptin levels in the blood decrease, the production of NPY is diminished, and the processes in adipose tissue shown in Figure 23-32 are reversed. Uncoupling is diminished,... 

Effects on lipid metabolism Adipose tissue responds within minutes to administration of insulin, which causes a significant reduc tion in the release of fatty acids ... 

Fatty liver refers to the abnormal accumulation of fat in hepatocytes. At the same time there is a decrease in plasma lipids and lipoproteins. Although many toxicants may cause lipid accumulation in the liver (Table 14.1), the mechanisms may be different. Basically lipid accumulation is related to disturbances in either the synthesis or the secretion of lipoproteins. Excess lipid can result from an oversupply of free fatty acids from adipose tissues or, more commonly, from impaired release of triglycerides from the liver into the plasma. Triglycerides are secreted from the liver as lipoproteins (very low density lipoprotein, VLDL). As might be expected, there are a number of points at which this process can be disrupted. Some of the more important ones are as follows (Figure 14.1) ... 

Chronic excessive nutrient intake leads to the deposition of fat, in not only its normal storage site, which is the adipose tissue, but also in liver and skeletal muscle. Nutrient excess also triggers an inflammatory response, with the release of inflammatory cytokines [tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and CRP]. These inflammatory mediators, along with the intracellular accumulation of lipid metabolites, lead to impaired insulin receptor signaling and defective metabolism in skeletal muscle and liver (37, 38). Nutrient excess also damages cells by generating reactive oxygen species, which results... 

New (de novo) fatty acids are synthesized from two-carbon acetyl units produced during metabolism. Two enzyme complexes, acetyl-coenzyme A carboxylase and fatty acid synthetase, work in concert to build up fatty acid chains, two carbons at a time, until released by the complex. The primer in plants and animals is essentially a two-carbon acetyl group and the fatty acid chains have even numbers of carbons. If the primer is a three-carbon propionate group, odd-number carbon chains result. Odd-number fatty acids are common in microbial lipids and also are synthesized de novo from propionic VFA by rumen bacteria and deposited in adipose tissue. The length of the fatty acid synthesized depends on the tissue. Palmitic acid is produced in the liver and adipose tissue, and shorter-chain fatty acids are also produced in the mammary glands (49). 

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