Adipose tissue glucose oxidation

In adipose tissue glucose uptake is diminished and triglyceride breakdown is increased. The fatty acids produced are exported via the plasma and are oxidized by other tissues, while the glycerol is used for gluconeogenesis in the liver. Muscle oxidizes mainly fatty acids and ketone bodies while the brain adapts to use ketone bodies rather than glucose as a major energy source. This ability of the brain to use ketone bodies reduces the requirement for amino acids as a source of glucose, and is a factor of importance in the conservation of body protein. 

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

Figure 27-1. Metabolic interrelationships between adipose tissue, the liver, and extrahepatic tissues. In extrahepatic tissues such as heart, metabolic fuels are oxidized in the following order of preference (1) ketone bodies, (2) fatty acids, (3) glucose. (LPL, lipoprotein lipase FFA, free fatty acids VLDL, very low density lipoproteins.)...

Fat is the major way we store energy. Fat is stored principally in adipose tissue and can be stored in virtually unlimited amounts. Fat is metabolized through (1 oxidation to acetyl-CoA and then through the TCA cycle, where it s burned completely to C02 to make ATP. Fat cannot be used to make carbohydrate because acetyl-CoA cannot be converted directly to precursors of glucose without losing its carbon atoms first (you ll see what this really means later). 

Fatty acids are oxidized in several tissues, including liver, muscle, and adipose tissue, by the pathway of P-oxidation. Neither erythrocytes nor brain can use fatty acids, and so continue to rely on glucose during normal periods of fastii. Erythrocytes lack mitochondria, and fatty acids do not cross the blood-hrain barrier efficiently. 

The FADHj and NADH are oxidized in the electron transport chain, providing ATP. In musde and adipose tissue, the acetyl CoA enters the citric acid cyde. In liver, the ATP may be used for gluconeogenesis, and the acetyl CoA (which cannot be converted to glucose) stimulates gluco-neogenesis by activating pyruvate carboxylase. 

Figure 8.23 Formation of glutamine from glucose and branched-chain amino adds in muscle and adipose tissue and probably in the lung. Oxoacids may also be released into blood for oxidation in the liver.

Figure 16.1 The glucose/fatty add cycle. The dotted Lines represent regulation. Glucose in adipose tissue produces glycerol 3-phosphate which enhances esterification of fatty acids, so that less are available for release. The effect is, therefore, tantamount to inhibition of lipolysis. Fatty acid oxidation inhibits pyruvate dehydrogenase, phosphofructokinase and glucose transport in muscle (Chapters 6 and 7) (Randle et al. 1963).

Figure 16.2 Redprocal relationship between the changes in the concentrations of glucose and fatty adds in blood during starvation in adult humans. As the glucose concentration decreases, fatty acids are released from adipose tissue (for mechanisms see Figure 16.4). The dotted line is an estimate of what would occur if fatty acid oxidation did not inhibit glucose utilisation. Such a decrease occurs if fatty acid oxidation in muscle is decreased by specific inhibitors.

Insulin also stimulates the storage of excess fuel as fat (Fig. 23-26). In the liver, insulin activates both the oxidation of glucose 6-phosphate to pyruvate via glycolysis and the oxidation of pyruvate to acetyl-CoA. If not oxidized further for energy production, this acetyl-CoA is used for fatty acid synthesis in the liver, and the fatty acids are exported as the TAGs of plasma lipoproteins (VLDLs) to the adipose tissue. Insulin stimulates TAG synthesis in adipocytes, from fatty acids released... 

Individuals with either type of diabetes are unable to take up glucose efficiently from the blood recall that insulin triggers the movement of GLUT4 glucose transporters to the plasma membrane of muscle and adipose tissue (see Fig. 12-8). Another characteristic metabolic change in diabetes is excessive but incomplete oxidation of fatty acids in the liver. The acetyl-CoA produced by JS oxidation cannot be completely oxidized by the citric acid cycle, because the high [NADH]/[NAD+] ratio produced by JS oxidation inhibits the cycle (recall that three steps convert NAD+ to NADH). Accumulation of acetyl-CoA leads to overproduction of the ketone bodies acetoacetate and /3-hydroxybutyrate, which cannot be used by extrahepatic tissues as fast as they are made in the liver. In addition to /3-hydroxybutyrate and acetoacetate, the blood of diabetics also contains acetone, which results from the spontaneous decarboxylation of acetoacetate ... 

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