Adipose tissue during fasting

As fatty acids are released from adipose tissue during fasting, they travel in the blood complexed with albumin. These fatty acids are oxidized by various tissues, particularly muscle. In the liver, fatty acids are transported into mitochondria... 

Fig. 36.10. Regulation of hormone-sensitive hpase (HSL) in adipose tissue. During fasting, the glucagon/insuhn ratio rises, causing cAMP levels to be elevated. Protein kinase A is activated and phosphorylates HSL, activating this enzyme. HSL-P initiates the mobilization of adipose triacylglycerol by removing a fatly acid (FA). Other lipases then act, producing fatty acids and glycerol. Insulin stimulates the phosphatase that inactivates HSL in the fed state.

Chylomicrons, large triglyceride-rich particles containing apolipoprotein B-48, B-lOO, and E, are formed from dietary fat solubilized by bile salts in intestinal mucosal cells (Fig. 21-2). Chylomicrons normally are not present in the plasma after a fast of 12 to 14 hours and are catabolized by lipoprotein lipase (LPL), which is activated by apolipoprotein C-II, in the vascular endothelium and hepatic lipase to form chylomicron remnants. The remnants that contain apolipoprotein E (see Fig. 21-2) are taken up by the remnant receptor, which may be an LDL-receptor-related protein, in the liver. Free cholesterol is liberated intracellularly after attachment to the remnant receptor. Chylomicrons also function to deliver dietary triglyceride to skeletal muscle and adipose tissue. During the catabolism of nascent chylomicrons to remnants, triglyceride is converted to free fatty acids and apolipoproteins A-I, A-II, A-IV (free in plasma), C-I, C-II, and... 

B. Role of Adipose Tissue During Prolonged Fasting... 

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. 

Because heptachlor epoxide is lipophilic, it is likely that the loss of adipose tissue, as may occur during fasting, will mobilize the stored compound and increase the rate of its elimination. However, this mobilization is also likely to temporarily increase the blood levels of heptachlor epoxide. Hence, any possible benefits due to a reduced body burden accompanying fat reduction would need to be balanced against potential harmful results due to the expected temporary increase in blood levels. 

During fasting, hormonal or metabolic modifications mobilise energy stored in adipose tissue as fat. Evaluation of different metabolite concentrations in blood provides insight into the different steps of fat metabolism. 

During a fast, the liver is flooded with fatty acids mobilized from adipose tissue. The resulting elevated hepatic acetyl CoA produced primarily by fatty acid degradation inhibits pyruvate dehydrogenase (see p. 108), and activates pyruvate carboxylase (see p. 117). The oxaloacetate thus produced is used by the liver for gluconeogenesis rather than for the TCA cycle. Therefore, acetyl Co A is channeled into ketone body synthesis. 

Triacylglycerol molecules stored in adipose tissue represent the major reserve of substrate providing energy during a prolonged fast. During such a fast ... 

Know ledge of metabolite levels in the bloodstream allows assessment of many changes in metabolism. For example, during fasting or exercise, the concentration of FFAs may increase from a basal level of about 0.5 mM to about 1.0 mM, With exercise, the concentration of lactic acid can increase from 1,0 to 2-0 mM- These changes a](jne, however, reveal little definite information about either the organs that produce the metabolites or the organs that use them. An increase in plasma FFAs could result from an increase in lipolysis in adipose tissues and their release into the bloodstream. This increase occurs W ith exercise, but an increase also can occur with a sudden decrease in their rate of use, as in a sudden cessation of exercise. 

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