Adipose tissue fasting state

CM and VLDL secreted by intestinal cells and VLDL synthesized and secreted in the liver have similar metabolic fates. After secretion into the blood, newly formed CM and VLDL take up apoprotein (apo-C) from HDL and are subsequently removed from the blood (plasma half-life of less than 1 h in humans [137]) primarily by the action of lipoprotein lipase (LPL). Lipoprotein lipase is situated mainly in the vascular bed of the heart, skeletal muscle, and adipose tissue and catalyzes the breakdown of core TG to monoglycerides and free fatty acids, which are taken up into adjacent cells or recirculated in blood bound to albumin. The activity of LPL in the heart and skeletal muscle is inversely correlated with its activity in adipose tissue and is regulated by various hormones. Thus, in the fasted state, TG in CM and VLDL is preferentially delivered to the heart and skeletal muscle under the influence of adrenaline and glucagon, whereas in the fed state, insulin enhances LPL activity in adipose tissue, resulting in preferential uptake of TG into adipose tissue for storage as fat. 

Because insulin normally inhibits lipolysis, a diabetic has an extensive lipolytic activity in the adipose tissue. As is seen in Table 21.4, plasma fatty acid concentrations become remarkably high. /3-Oxidation activity in the liver increases because of a low insulin/glucagon ratio, acetyl-CoA carboxylase is relatively inactive and acyl-CoA-camitine acyltransferase is derepressed. /3-Oxidation produces acetyl-CoA which in turn generates ketone bodies. Ketosis is perhaps the most prominent feature of diabetes mellitus. Table 21.5 compares ketone body production and utilization in fasting and in diabetic individuals. It may be seen that, whereas in the fasting state ketone body production is roughly equal to excretion plus utilization, in diabetes this is not so. Ketone bodies therefore accumulate in diabetic blood. 

Figure 6-9. Regulation of triacylglycerol stores in adipose tissue. Left = in the fed state. Right = in the fasted state. TG = triacylglycerol FA = fatty acid LPL = lipoprotein lipase DHAP = dihydroxyacetone phosphate = stimulated by circled TG = triacylglycerol of chylomicrons and VLDL.

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.

When plasma insulin levels are low, as in the fasting state, GH enhances fatty acid oxidation to acetyl CoA. This effect in concert with the increased flow of fatty acids from adipose tissue enhances ketogenesis. The increased amount of glycerol reaching the liver as a consequence of enhanced lipolysis acts as a substrate for gluco-... 

Describe how the blood-glucose level is controlled by the liver in response to glucagon and insulin in well-fed, early fasting, and refed states. Discuss the contributions of muscle and adipose tissue to the regulation of the blood-glucose level. 

Ingestion, absorption and deposition of fat into adipose tissue is considerably high (i.e. 60-100 g/day). In the post-absorptive state, 50-90% of the body s total energy needs, including that of the heart, is met by free fatty acids delivered from adipose tissue. The total movement of fatty acids from one tissue to the other is voluminous and fast, while that of cholesterol and phos-phohpids is less and rather slow. The daily turnover of cholesterol, representing the transfer from the catabohc to the anabolic sites within the body, approximates 1 g. More than 90% of the cholesterol leaves the body in the feces as bile acids and predominantly as cholic acid. 

In men with atherogenic dyslipemia of the insulin resistance syndrome, plasma C-reactive protein (CRP) levels showed positive correlations with body fat mass, waist girth, visceral adipose tissue, and insulin levels (measured in the fasting state and after a 75-g oral glucose load), but not with plasma lipoprotein levels (119). 

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