Tissue-Specific Metabolism: The Division of Labor:- Adipose Tissue Stores and Supplies Fatty Acids
Adipose tissue, which consists of adipocytes (fat cells) (Fig. 1), is amorphous and widely distributed in the body: under the skin, around the deep blood vessels, and in the abdominal cavity. It typically makes up about 15% of the mass of a young adult human, with approximately 65% of this mass in the form of triacylglycerols. Adipocytes are metabolically very active, responding quickly to hormonal stimuli in a metabolic interplay with the liver, skeletal muscles, and the heart. Like other cell types, adipocytes have an active glycolytic metabolism, use the citric acid cycle to oxidize pyruvate and fatty acids, and carry out oxidative phos phorylation. During periods of high carbohydrate intake, adipose tissue can convert glucose (via pyruvate and acetyl-CoA) to fatty acids, convert the fatty acids to TAGs, and store them as large fat globules—although, in humans, much of the fatty acid synthesis occurs in hepatocytes. Adipocytes store TAGs arriving from the liver and from the intestinal tract (carried in chylomicrons), particularly after meals rich in fat. When fuel demand rises, lipases in adipocytes hydrolyze stored TAGs to release free fatty acids, which can travel in the bloodstream to skeletal muscles and the heart. The release of fatty acids from adipocytes is greatly accelerated by epinephrine, which stimulates the cAMP-dependent phosphorylation of perilipin; this gives triacylglycerol lipase access to TAGs in the lipid droplet. The hormone-sensitive lipase is also stimulated by phosphorylation, but this is not the main cause of increased lipolysis. Insulin counterbalances this effect of epinephrine, decreasing the activity of triacylglycerol lipase.
FIGURE 1 Scanning electron micrograph of human adipocytes. In fat tissues, capillaries and collagen fibers form a supporting network around spherical adipocytes. Almost the entire volume of these metabolically active cells is taken up by fat droplets.
The breakdown and synthesis of TAGs in adipose tissues constitute a substrate cycle; up to 70% of the fatty acids released by triacylglycerol lipase are reesterified in adipocytes, re-forming TAGs. that such substrate cycles allow fine regulation of the rate and direction of flow of intermediates through a bidirectional pathway. In adipose tissue, glycerol liberated by triacylglycerol lipase cannot be reused in the synthesis of TAGs, because adipocytes lack the enzyme glycerol kinase. Instead, the glycerol phosphate required for TAG synthesis is made from pyruvate by glyceroneogenesis, involving the cytosolic enzyme PEP carboxykinase. This enzyme is one target of the drugs (thiazolidinediones) used in the treat ment of type II diabetes, raising the possibility that defective regulation of cytosolic PEP carboxykinase in fat tissue may be a causative factor in type II diabetes. Human infants, and many hibernating animals, have adipose tissue called brown fat, which is specialized to generate heat rather than ATP during oxidation of fatty acids. Adult humans have very little brown fat tissue.
