Adipose tissue metabolic activities

Freinkel (1961) has reported that commercial TSH, mouse tumor, TSH, and the most highly purified preparations of beef TSH available, all increase the release of free fatty acid by epididymal adipose tissue from normal fed rats incubated in an albumin-containing medium. This effect of TSH was obtained with concentrations of 0.01-1.0 USP unit per milliliter. The tissue content of free fatty acid also rose during incubation. Heating TSH for 3 minutes at pH 2 caused a profound reduction in its effects upon fatty acid relea.se and other aspects of adipose tissue metabolism. Similar treatment of oxycellulose-adsorbed adrenocorticotropin did not diminish the in vitro activity of this hormone in adipose tissue. Moreover, the effect of TSH on the release of free fatty acids by adipose tissue was not dependent upon the presence of ionic calcium in the medium, although this ion is required if the effects of ACTH are to be demonstrated (Lopez et al., 1959). The effects of TSH in adipose tissue, therefore, are probably not the result of ACTH contamination. 

Under the influence of ACTH, free fatty acids and glycerol concentrations increase in adipose tissue. ACTH stimulates lipolysis in adipose tissue by activating a hormone-sensitive lipase. However, ACTH does not act directly on the lipase. There are at least two other intermediate messengers adenylate cyclase and cyclic adenylate. The molecular mechanism of action of ACTH on lipolysis will be discussed in more detail in the section devoted to adipose tissue metabolism. 

The GI absorption of the dmg after po adrninistration is slow and variable with estimates ranging from 20—55%. Once absorbed, 96% of the dmg is bound to plasma proteins and other tissues on the body. Whereas peak plasma concentrations may be achieved in 3—7 h, the onset of antiarrhythmic action may occur in 2—3 days or more. This may result, in part, from distribution to and concentration of the dmg in adipose tissue, Hver, spleen, and lungs. Therapeutic plasma concentrations are 1—2 p.g/mL, although there appears to be no correlation between plasma concentration and antiarrhythmic activity. The plasma half-life after discontinuation of the dmg varies from 13—103 days. The dmg is metabolized in the Hver and the principal metaboHte is desethylamiodarone. The primary route of elimination is through the bile. Less than 1% of the unchanged dmg is excreted in the urine. The dmg can also be eliminated in breast milk and through the skin (1,2). 

Insulin appears to activate a process that helps glucose molecules enter the cells of striated muscle and adipose tissue Figure 49-1 depicts normal glucose metabolism. Insulin also stimulates die synthesis of glycogen by die liver. In addition, insulin promotes protein syntiiesis and helps the body store fat by preventing its breakdown for energy. 

Figure 25-7. Metabolism of adipose tissue. Hormone-sensitive lipase is activated by ACTH, TSH, glucagon, epinephrine, norepinephrine, and vasopressin and inhibited by insulin, prostaglandin E, and nicotinic acid. Details of the formation of glycerol 3-phosphate from intermediates of glycolysis are shown in Figure 24-2. (PPP, pentose phosphate pathway TG, triacylglycerol FFA, free fatty acids VLDL, very low density lipoprotein.)...

In adipose tissue, the effect of the decrease in insulin and increase in glucagon results in inhibition of lipo-genesis, inactivation of lipoprotein lipase, and activation of hormone-sensitive lipase (Chapter 25). This leads to release of increased amounts of glycerol (a substrate for gluconeogenesis in the liver) and free fatty acids, which are used by skeletal muscle and liver as their preferred metabolic fuels, so sparing glucose. 

The regulation of fat metabolism is relatively simple. During fasting, the rising glucagon levels inactivate fatty acid synthesis at the level of acetyl-CoA carboxylase and induce the lipolysis of triglycerides in the adipose tissue by stimulation of a hormone-sensitive lipase. This hormone-sensitive lipase is activated by glucagon and epinephrine (via a cAMP mechanism). This releases fatty acids into the blood. These are transported to the various tissues, where they are used. 

In adipose tissue, insulin stimulation suppresses triglyceride hydrolysis (to free fatty acids and glycerol) by activating cAMP phosphodiesterase (cAMP PDE). Cyclic AMP, (3, 5 cAMP), is required to stimulate hormone sensitive lipase (HSL), the enzyme which hydrolyses triglyceride within adipocytes PDE converts active 3, 5 cAMP to inactive 5 AMP thus preventing the stimulation of HSL. The net effect of insulin on lipid metabolism is to promote storage. 

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