Regulation of Energy Release from Triglycerides

Regulation of Energy Release from Triglycerides

Carbohydrates Are Preferred over Fats for Energy When Excess Carbohydrates Are Available. When excess quantities ofcarbohydrates are available in the body, carbohydrates are used preferentially over triglycerides for energy. There are several reasons for this “fat-sparing” effect of carbohydrates. One of the most important is the fol-lowing:The fats in adipose tissue cells are present in two forms: stored triglycerides and small quantities of free fatty acids. They are in constant equilibrium with each other. When excess quantities of a-glycerophosphate are present (which occurs when excess carbohydrates are available), the excess a-glycerophosphate binds the free fatty acids in the form of stored triglycerides. As a result, the equilibrium between free fatty acids and triglycerides shifts toward the stored triglycerides; consequently, only minute quantities of fatty acids are available to be used for energy. Because a-glycerophosphate is an important product of glucose metabolism, the availability of large amounts of glucose automatically inhibits the use of fatty acids for energy.

Second, when carbohydrates are available in excess, fatty acids are synthesized more rapidly than they are degraded. This effect is caused partially by the large quantities of acetyl-CoA formed from the carbohy-drates and by the low concentration of free fatty acids in the adipose tissue, thus creating conditions appropri-ate for the conversion of acetyl-CoA into fatty acids.

An even more important effect that promotes the conversion of carbohydrates to fats is the following: The first step, which is the rate-limiting step, in the synthesis of fatty acids is carboxylation of acetyl-CoA to form malonyl-CoA. The rate of this reaction is controlled primarily by the enzyme acetyl-CoA carboxylase, the activity of which is accelerated in the presence of inter-mediates of the citric acid cycle. When excess carbohy-drates are being used, these intermediates increase, automatically causing increased synthesis of fatty acids.

Thus, an excess of carbohydrates in the diet not only acts as a fat-sparer but also increases fat stores. In fact, all the excess carbohydrates not used for energy or stored in the small glycogen deposits of the body are converted to fat for storage.

Acceleration of Fat Utilization for Energy in the Absence of Car- bohydrates. All the fat-sparing effects of carbohydratesare lost and actually reversed when carbohydrates are not available. The equilibrium shifts in the opposite direction, and fat is mobilized from the adipose cells and used for energy in place of carbohydrates.

Also important are several hormonal changes that take place to promote rapid fatty acid mobilization from adipose tissue. Among the most important of these is a marked decrease in pancreatic secretion of insulin caused by the absence of carbohydrates. This not only reduces the rate of glucose utilization by the tissues but also decreases fat storage, which further shifts the equilibrium in favor of fat metabolism in place of carbohydrates.

Hormonal Regulation of Fat Utilization. At least seven ofthe hormones secreted by the endocrine glands have significant effects on fat utilization. Some important hormonal effects on fat metabolism—in addition to insulin lack, discussed in the previous paragraph—arenoted here.

Probably the most dramatic increase that occurs in fat utilization is that observed during heavy exercise. This results almost entirely from release of epinephrine and norepinephrine by the adrenal medullae during exer-cise, as a result of sympathetic stimulation. These two hormones directly activate hormone-sensitive triglyc-eride lipase, which is present in abundance in the fatcells, and this causes rapid breakdown of triglycerides and mobilization of fatty acids. Sometimes the free fatty acid concentration in the blood of an exercising person rises as much as eightfold, and the use of these fatty acids by the muscles for energy is correspondingly increased. Other types of stress that activate the sym-pathetic nervous system can also increase fatty acid mobilization and utilization in a similar manner.

Stress also causes large quantities of corticotropin to be released by the anterior pituitary gland, and this causes the adrenal cortex to secrete extra quantities of glucocorticoids. Both corticotropin and glucocorticoidsactivate either the same hormone-sensitive triglyceride lipase as that activated by epinephrine and norepi-nephrine or a similar lipase. When corticotropin and glucocorticoids are secreted in excessive amounts for long periods, as occurs in the endocrine condition called Cushing’s disease, fats are frequently mobilized to such a great extent that ketosis results. Corticotropin and glucocorticoids are then said to have a ketogenic effect.Growth hormone has an effect similar to but weakerthan that of corticotropin and glucocorticoids in activating hormone-sensitive lipase. Therefore, growth hormone can also have a mild ketogenic effect.

Finally, thyroid hormone causes rapid mobilization of fat, which is believed to result indirectly from an increased overall rate of energy metabolism in all cells of the body under the influence of this hormone. The resulting reduction in acetyl-CoA and other intermedi-ates of both fat and carbohydrate metabolism in the cells is a stimulus to fat mobilization.

Obesity

Obesity means deposition of excess fat in the body. It is caused by the ingestion of greater amounts of food than can be used by the body for energy. The excess food, whether fats, carbohydrates, or proteins, is then stored almost entirely as fat in the adipose tissue, to be used later for energy.

Strains of rats have been found in which hereditaryobesity occurs. In at least one of these, the obesity iscaused by ineffective mobilization of fat from the adipose tissue by tissue lipase, while synthesis and storage of fat continue normally. Such a one-way process causes progressive enhancement of the fat stores, resulting in severe obesity.