Adipose tissue hormones

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.)...

The underlying mechanism may involve the adipose tissue hormone leptin or immune modulators such as tumor necrosis factor alfa. 

Guerre-Milo M. Adipose tissue hormones. J Endocrinol Invest 2002 25(10) 855 61. 

J.K. Huttunen and D. Steinberg, Activation and phosphorylation of purified adipose tissue hormone-sensitive lipase by cyclic AMP-dependent protein kinase, Biochim. Biophys. Acta, 1971, 239, 411-427. 

M. Guerre-Milo, Adipose tissue hormones, J. Endocrinol. Invest. 25 (10) (2002) 855-861. 

In Type I diabetes mellitus, there is a severe deficiency (or total absence) of insulin due to an autoimmune attack on the cells that produce insulin, pancreatic j8-cells. The absence of insulin produces a deficiency in adipose tissue lipoprotein lipase. This causes sluggish catabolism of VLDL and leads to hypertriglyceridemia. Another mechanism by which insulin deficiency promotes increased VLDL levels is the failure to inhibit the activity of adipose tissue hormone-sensitive lipase. This enzyme hydrolyzes cytoplasmic triglyceride droplets. The fatty acids then go to the liver, where they are re-esterified to form triglycerides. These triglycerides are exported on VLDL particles. Since adipose tissue-derived fatty acids are an important substrate for hepatic VLDL triglycerides, the failure to suppress adipose tissue lipolysis is an important contributor to the enhanced rate of VLDL triglyceride secretion. 

The hypertriglyceridemia of Type II diabetes, unlike that which is found with Type I diabetes, is not due to excessive adipocyte lipolysis. This is because only a small level of insulin action is required to suppress excessive adipose tissue hormone-sensitive lipase activity. In Type II diabetes, there is insufficient adipose tissue lipoprotein lipase and excessive hepatic triglyceride synthesis. Thus, inefficient VLDL triglyceride catabolism and excessive VLDL triglyceride secretion both contribute to the excess VLDL in Type II diabetes. 

Severson, D. L., Khoo, J. C., and Steinberg, D., 1977, Role of phosphoprotein phosphatases in reversible deactivation of chicken adipose tissue hormone-sensitive lipase, /. Biol. Chem. 252 1484. 

Reports have appeared in the Hterature of the use of human growth hormone in older men. It has been proposed that a reduction in growth hormone in old age is responsible for increased adipose tissue, loss of lean body mass, and thinning of skin. Current studies conducted on older men indicate the hormone reverses these effects. In the parameters studied the patients resembled those of persons 10 —20 years younger (70). 

Insulin is a peptide hormone, secreted by the pancreas, that regulates glucose metabolism in the body. Insufficient production of insulin or failure of insulin to stimulate target sites in liver, muscle, and adipose tissue leads to the serious metabolic disorder known as diabetes mellitus. Diabetes afflicts millions of people worldwide. Diabetic individuals typically exhibit high levels of glucose in the blood, but insulin injection therapy allows diabetic individuals to maintain normal levels of blood glucose. 

Hormones Signal the Release of Fatty Acids from Adipose Tissue... 

FIGURE 24.2 Liberation of fatty acids from triacylglycerols in adipose tissue is hormone-dependent. 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Uptake of LCFAs across the lipid-bilayer of most mammalian cells occurs through both a passive diffusion of LCFAs and a protein-mediated LCFA uptake mechanism. At physiological LCFA concentrations (7.5 nM) the protein-mediated, saturable, substrate-specific, and hormonally regulated mechanism of fatty acids accounts for the majority (>90%) of fatty acid uptake by tissues with high LCFA metabolism and storage such as skeletal muscle, adipose tissue, liver,... 

A principal action of insufin in adipose tissue is to inhibit the activity of hormone-sensitive lipase, reducing the release not only of free fatty acids but of glycerol as well. Adipose tissue is much more sensitive to insulin than are many other tissues, which points to adipose tissue as a major site of insufin action in vivo. 

Otfier fiormones accelerate tfie release of free fatty acids from adipose tissue and raise tfie plasma free fatty acid concentration by increasing the rate of lipolysis of the triacylglycerol stores (Figure 25—8). These include epinephrine, norepinephrine, glucagon, adrenocorticotropic hormone (ACTH), a- and P-melanocyte-stimulat-ing hormones (MSH), thyroid-stimulating hormone (TSH), growth hormone (GH), and vasopressin. Many of these activate the hormone-sensitive hpase. For an optimal effect, most of these lipolytic processes require the presence of glucocorticoids and thyroid hormones. These hormones act in a facilitatory or permissive capacity with respect to other lipolytic endocrine factors. 

Figure 25-8. Control of adipose tissue lipolysis. (TSH, thyroid-stimulating hormone FFA, free fatty acids.) Note the cascade sequence of reactions affording amplification at each step. The lipolytic stimulus is "switched off" by removal of the stimulating hormone the action of lipase phosphatase the inhibition of the lipase and adenylyl cyclase by high concentrations of FFA the inhibition of adenylyl cyclase by adenosine and the removal of cAMP by the action of phosphodiesterase. ACTFI,TSFI, and glucagon may not activate adenylyl cyclase in vivo, since the concentration of each hormone required in vitro is much higher than is found in the circulation. Positive ( ) and negative ( ) regulatory effects are represented by broken lines and substrate flow by solid lines.

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. 

Adipose tissue Storage and breakdown of triacylglyc-erol Esterification of fatty acids and lipolysis lipogenesis Glucose, lipoprotein triacylglycerol Free fatty acids, glycerol Lipoprotein lipase, hormone-sensitive lipase... 

In addition to fiber and carbohydrate content, protein intake from legumes may have weight-loss benefits for obese individuals just because proteins enhance post-meal satiety (Rolls, 1995). However, a possible specific role for phytoestrogens in obesity has been postulated through the modulation of the satiety response, a neuroendocrine mechanism controlled by leptin (a hormone secreted by adipose tissue and already known to be regulated by... 

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