Adipose tissue fatty acid release from, regulation

Newsholme and Gevers (1967) have proposed that an additional form of amplification and control of a pathway may be obtained if a substrate cycle is operative in the pathway, e.g., a cycle, between fruc-tose-6-phosphate and fructose-1,6-diphosphate, which may participate in the regulation of glycolytic flux in muscle. A cycle between triglycerides and fatty acids, which appears to control the rate of fatty acid release from adipose tissue, may also occur (Newsholme and Crabtree, 1976). 

Various situations yield to induction of fatty acid catabolism in the liver such as birth which corresponds to a transition in energy source from a carbohydrate-rich to a lipid-rich regimen fasting, which is associated with free fatty acid release in the blood due to lipolysis of the adipose tissue as well as exposure to various xenobiotics. Several biochemical mechanisms exist to rapidly control the activity of the different enzymes involved in fatty acid oxidation. However, the transcriptional regulation of the expression of these enzymes is an additional level of control necessary for long-term maintenance of the organism energy balance. 

Figure 7.9 The degradation of triaq/lglycerol in adipose tissue to fatty acids and glycerol. The figure indicates the progressive release of fatly acids and the types of fatty acid that are usually present at each position and, therefore, released from each position as the triacylglycerol molecule. Sat. - Saturated. A lipase that is not regulated by hormones is also present is adipose tissue. It is continually active. Its role is described below.

Changes in the blood levels of these hormones all contribute to regulation of blood glncose level in several conditions. After a meal glucose utilisation is increased, since insulin stimulates glucose uptake by muscle and inhibits release of fatty acids from adipose tissue. Physical activity... 

The Release of Fatty Acids from Adipose Tissue Is Regulated... 

The release of fatty acids from adipose tissue is regulated by the rate of hydrolysis of triacylglycerol and the rate of esterification of acyl-CoA with glycerol 3-phosphate. The rate of hydrolysis is stimulated by hormones that bind to cell-surface receptors and stimulate adenylate cyclase (which catalyzes the production of cAMP from ATP). Hormone-sensitive lipase (Sec. 13.4) can exist in two forms, one of which exhibits very low activity and a second which is phosphorylated and has high activity. Before hormonal stimulation of adenylate cyclase, the low-activity lipase predominates in the fat cell. Stimulation of protein kinase by an increase in cAMP concentration leads to phosphorylation of the low-activity lipase. An increase in the rate of hydrolysis of triacylglycerol and the release of fatty acids from the fat cell follows. This leads to a greater utilization of fatty acids by tissues such as heart, skeletal muscle, and liver. 

Ketogenesis in the liver. All reactions occur in mitochondria the rate-controlling reactions (not shown) are release of fatty acids from adipose tissue and uptake of acyl-CoA into mitochondria, in particular, the CPTI reaction (see Figure 18-1). Acetoacetyl-CoA may regulate ketogenesis by inhibiting the transferase and the synthase. 

The entire process of heat generation from brown fat, called nonshivering thermogenesis, is regulated by norepinephrine. (In shivering thermogenesis, heat is produced by nonvoluntary muscle contraction.) Norepinephrine, a neurotransmitter released from specialized neurons that terminate in brown adipose tissue, initiates a cascade mechanism that ultimately hydrolyzes fat molecules. The fatty acid products of fat hydrolysis activate the uncoupler protein. Fatty acid oxidation continues until the norepinephrine signal is terminated or the cell s fat reserves are depleted. 

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