Mobilization of Fat from Adipose Tissue | Lipid Metabolism

In this article we will discuss about the Mobilization of Fat from Adipose Tissue and its Metabolism:- 1. Meaning of Adipose Tissue 2. Influence of Hormones on Adipose Tissue 3. Role of Brown Adipose Tissue.

Meaning of Adipose Tissue:

Adipose tissue is the main store of triacylglycerol in the body. Adipose tissue was previously consid­ered an inert storage depot for fat. But according to recent investigations, this tissue is not static. It per­forms important functions in the metabolism of lipids.

This tissue is under nervous control and con­ditions which cause sympathetic discharge result in the liberation of un-esterified fatty acids and thus a loss of fat. Mobilization of fat is inhibited by denervation. Different types of adipose tissue (e.g., white and brown) exhibit differences in metabo­lism.

Both the glycolytic sequence of reactions and the pentose-shunt pathway are operative in adipose tissue. Triacylglycerol is synthesized from acyl-CoA and glycerol-3-phosphate in adipose tissue.

Since the activity of glycerokinase is low in adi­pose tissue, glycerol cannot be utilized to any great extent in the esterification of acyl-CoA to form triacylglycerol. For the provision of glycerol-3-phosphate, adipose tissue is dependent on a sup­ply of glucose.

Triacylglycerol is hydrolyzed by a hormone-sensitive lipase to form free fatty acids and glycerol. But the tissue cannot utilize glycerol readily. Therefore, glycerol diffuses out into the plasma and it is utilized by liver and kidney where active glycerokinase is present.

The free fatty acids can be resynthesized in adipose tissue to acyl-CoA by acyl-CoA synthase and re-esterified with glycerol- 3-phosphate to form triacylglycerol. Thus, there is a continued cycle of lipolysis and re-esterification within the adipose tissue.

When the rate of re-es­terification is not sufficient to cope with the rate of lipolysis, free fatty acids accumulate and diffuse into the plasma. Thus, the level of free fatty acid (FFA) rises in the plasma.

In starvation or in diabetes mellitus, the avail­ability of glucose in adipose tissue is reduced and less glycerol-3-phosphate is formed. As a result, the rate of lipolysis exceeds the rate of esterifica­tion with the accumulation of free fatty acids which are released into the plasma.

In adipose tissue, glucose is oxidized to CO₂ via citric acid cycle, oxidized in the HMP shunt and converted to long chain fatty acids and can form acylglycerol via glycerol-3-phosphate. When glucose utilization is reduced, the greater portion of the glucose is utilized to form glycerol-3-phos­phate and acylglycerol.

Influence of Hormones on Adipose Tissue:

A. Insulin:

1. It inhibits the release of free fatty acids from adipose tissue, enhances lipogenesis and the synthesis of acylglycerol and in­creases the oxidation of glucose to CO₂ via HMP-shunt.

2. It inhibits the activity of hormone-sensitive lipase and reduces the release of free fatty acids as well as glycerol.

3. Insulin, nicotinic acid and prostaglandin E₁ inhibit the synthesis of cAMP depress­ing adenylate cyclase or stimulating phos­phodiesterase. Prostaglandin E₁ in low concentration causes the release of catecholamine’s resulting in the increase in free fatty acid mobilization.

B. ACTH, MSH, TSH, Growth Hormone, Vasopressin, Epinephrine, Norepinephrine and Glucagon:

1. These hormones accelerate the release of free fatty acids from adipose tissue by increasing the rate of lipolysis of the triacyl­glycerol stores.

2. Many of these activate the hormone-sen­sitive lipase and increase glucose utiliza­tion.

3. Glucocorticoids and thyroid hormones do not increase lipolysis but the presence of these hormones in the lipolytic processes is essential. Thyroid hormone inhibits phosphodiesterase activity. The lipolytic effect of growth hormone in presence of glucocorticoids is slow.

4. These hormones stimulate adenylate cy­clase for the formation of cAMP from ATP and this cAMP stimulates the protein ki­nase which converts inactive hormone- sensitive triacylglycerol lipase into the active lipase.

In addition to the hormone-sensitive triacylglycerol lipase, the adi­pose tissue contains diacylglycerol and mono-acylglycerol lipases which are more active than the hormone-sensitive triacylglycerol lipase and catalyze the rate limiting step in lipolysis.

Lipolysis is controlled by the amount of cAMP present in the tissue. cAMP is degraded to 5′-AMP by the enzyme cyclic 3′, 5′- nucleotide phosphodi­esterase. This enzyme is inhibited by methyl xanthine’s such as caffeine and theophylline.

There­fore, drinking of coffee or the administration of caf­feine causes the high elevation of plasma-free fatty acids in humans. The sympathetic nervous system, through lib­eration of norepinephrine, plays a central role in the mobilization of free fatty acids by exerting a tonic influence.

Role of Brown Adipose Tissue:

1. Brown adipose tissue promotes thermo- genesis. The tissue is present in small amounts in newborn animal and in human infants around the neck. This is very ac­tive in newborn animals. It contains high content of mitochondria, cytochromes and a well-developed blood supply.

2. Its oxygen consumption is very high with the conversion of glucose and fatty acids to CO₂.

3. Lipolysis is active; but re-esterification takes place with glycerol because of the presence of significant amounts of glycerokinase in this tissue. Norepine­phrine liberated from sympathetic nerve endings increases lipolysis in this tissue.

4. Oxidation produces much heat and little free energy is tapped in ATP.

5. Free glycerol from lipolysis is converted to glycerol-3-phosphate by glycerokinase and is oxidized directly in the tissue.