Adipose Tissue Lipolysis Is Inhibited by Insulin The rate of release of FFA from adipose tissue is affected by many hormones that influence either the rate of esterification or the rate of lipolysis. Insulin inhibits the release of FFA from adipose tissue, which results in a fall in circulating plasma FFA. Insulin also enhances lipogenesis and the syn thesis of acylglycerol and increases the oxidation of glucose to CO₂ via the pentose phosphate pathway. All of these effects are dependent on the presence of glucose and can be explained, to a large extent, on the basis of the ability of insulin to enhance the uptake of glucose into adipose cells via the GLUT 4 transporter. In addition, insulin increases the activity of the enzymes pyruvate dehydrogenase, acetyl-CoA carboxylase, and glycerol phosphate acyltransferase, reinforcing the effects of increased glucose uptake on the enhancement of fatty acid and acylglycerol synthesis. These three enzymes are regulated in a coordinate manner by phosphorylation–dephosphorylation mechanisms.

Another principal action of insulin in adipose tissue is to inhibit the activity of hormone-sensitive lipase, reducing the release not only of FFA but also of glycerol. Adipose tissue is much more sensitive to insulin than many other tissues, and is thus a major site of insulin action in vivo.

Several Hormones Promote Lipolysis Other hormones accelerate the release of FFA from adipose tissue and raise the plasma-free fatty acid concentration by increasing the rate of lipolysis of the triacylglycerol stores (Figure 1). These include epinephrine, norepinephrine, glucagon, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), growth hormone (GH). Many of these activate hormone-sensitive lipase. 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.

Fig1. Control of adipose tissue lipolysis.Hormone-sensitive lipase is activated when phosphorylated by cAMP-dependent protein kinase. cAMP is generated by adenylate cyclase and degraded by phosphodiesterase. 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. The stimulatory effects of epinephrine and norepinephrine on adenylate cyclase are promoted by β-adrenergic blockers and inhibited by thyroid hormone. Similarly, methylxanthines block the inhibition of the enzyme by adenosine. ⊕ , positive and ⊖, negative regulatory effects. (2-MAGL, 2-monoacylglycerol lipase; ACTH, adrenocorticotropin hormone; FFA, free fatty acids; GH, growth hormone; TSH, thyroid-stimulating hormone.)

The hormones that act rapidly in promoting lipolysis, that is, catecholamines (epinephrine and norepinephrine), do so by stimulating the activity of adenylyl cyclase, the enzyme that converts ATP to cAMP. The mechanism is analogous to that responsible for hormonal stimulation of glycogenolysis. cAMP, by stimulating cAMP-dependent protein kinase, activates hormone-sensitive lipase. Thus, processes which destroy or preserve cAMP influence lipolysis. cAMP is degraded to 5′-AMP by the enzyme cyclic 3′,5′-nucleotide phosphodiesterase. This enzyme is inhibited by methylxanthines such as caffeine and theophylline. Insulin antagonizes the effect of the lipolytic hormones. Lipolysis appears to be more sensitive to changes in concentration of insulin than are glucose utilization and esterification. The antilipolytic effects of insulin, as well as those of nicotinic acid and prostaglandin E1 which also act in this way, are accounted for by inhibition of the synthesis of cAMP at the adenylyl cyclase site, acting through a Gi protein. Insulin also stimulates the phosphodiesterase and the lipase phosphatase that inactivates hormone sensitive lipase. The effect of growth hormone in promoting lipolysis is dependent on synthesis of proteins involved in the formation of cAMP. Glucocorticoids promote lipolysis via syn thesis of new lipase protein by a cAMP-independent pathway, which may be inhibited by insulin, and also by promoting transcription of genes involved in the cAMP signal cascade. These findings help to explain the role of the pituitary gland and the adrenal cortex in enhancing fat mobilization. The sympathetic nervous system, through liberation of norepinephrine in adipose tissue, plays a central role in the mobilization of FFA.

Thus, the increased lipolysis caused by many of the factors described earlier can be reduced or abolished by denervation of adipose tissue or by ganglionic blockade.

Perilipin Regulates the Balance Between Triacylglycerol Storage & Lipolysis in Adipocytes

Perilipin, a protein involved in the formation of lipid droplets in adipocytes, inhibits lipolysis in basal conditions by preventing access of the lipase enzymes to the stored triacylglycerols. On stimulation with hormones which promote triacylglycerol degradation, however, the protein becomes phosphorylated and changes its conformation, exposing the lipid droplet sur face to hormone-sensitive lipase and thus promoting lipolysis. Perilipin, therefore, enables the storage and breakdown of tri acylglycerol to be coordinated according to the metabolic needs of the body.

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مواضيع ذات صلة

Brown Adipose Tissue Promotes Thermogenesis

Adipose Tissue is The Main Store of Triacylglycerol in The Body

Classification of Proteins

Precipitation Reactions of Proteins

Study of Protein Structure

Imbalance in the Rate of Triacylglycerol Formation & Export Causes Fatty Liver

The Liver Plays A Central Role in Lipid Transport & Metabolism

HDL Takes Part in Both Lipoprotein Triacylglycerol & Cholesterol Metabolism

Tertiary Structure of Proteins

Secondary Structure of Proteins

Primary Structure of Proteins

Chylomicrons & Very-low Density Lipoproteins are Rapidly Catabolized