Free fatty acids metabolism

Groop, L. C., Bonadonna, R. C., DelPrato, S., Ratheiser, K, Zyck, K Ferrannini, E., and DeFronzo, R A. (1989). Glucose and free fatty acid metabolism in non-insulin-depend-eni diabetes mellitus. . Clin, invest. Hi, 205-213. 

A. Basu, et ah. Systemic and regional free fatty acid metabolism in type 2 diabetes, Am. J. Physiol. Endocrinol. Metab., 2001, 280, 1000-1006. 

S.E. Meek, et al.. Insulin regulation of regional free fatty acid metabolism. Diabetes, 1999, 48, 10-14. 

Koutsari C, Jensen MD. Thematic review series patient-oriented research. Free fatty acid metabolism... 

Michaels, G. A method for the determination of plasma glycerides and free fatty acids. Metabolism 11, 833 (1962). 

PPARy is a transcription factor which controls the expression of enzymes and proteins involved in fat and glucose metabolism. More importantly, stimulation of this receptor induces differentiation of preadipocytes to adipose cells. It is believed that the formation of additional, small fat cells lowers free fatty acids and hepatic triglycerides, thereby collecting insulin resistance. 

Insulin resistance occurs when the normal response to a given amount of insulin is reduced. Resistance of liver to the effects of insulin results in inadequate suppression of hepatic glucose production insulin resistance of skeletal muscle reduces the amount of glucose taken out of the circulation into skeletal muscle for storage and insulin resistance of adipose tissue results in impaired suppression of lipolysis and increased levels of free fatty acids. Therefore, insulin resistance is associated with a cluster of metabolic abnormalities including elevated blood glucose levels, abnormal blood lipid profile (dyslipidemia), hypertension, and increased expression of inflammatory markers (inflammation). Insulin resistance and this cluster of metabolic abnormalities is strongly associated with obesity, predominantly abdominal (visceral) obesity, and physical inactivity and increased risk for type 2 diabetes, cardiovascular and renal disease, as well as some forms of cancer. In addition to obesity, other situations in which insulin resistance occurs includes... 

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.)...

Increased Glucose Metabolism Reduces the Output of Free Fatty Acids... 

On consideration of the profound derangement of metabolism in diabetes mellitus (due in large part to increased release of free fatty acids from the depots) and the fact that insuHn to a large extent corrects the condi-... 

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.)...

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. 

Caprio S et al Oxidative fuel metabolism during mild hypoglycemia critical role of free fatty acids. Am J Physiol... 

Glucose derived from muscle glycogen and metabolized by anaerobic glycolysis is the major fuel source. Blood glucose and free fatty acids are the major fuel sources. 

Experiments with monkeys given intramuscular injections of a mineral oil emulsion with [l-14C] -hexa-decane tracer provide data illustrating that absorbed C-16 hydrocarbon (a major component of liquid petrolatum) is slowly metabolized to various classes of lipids (Bollinger 1970). Two days after injection, substantial portions of the radioactivity recovered in liver (30%), fat (42%), kidney (74%), spleen (81%), and ovary (90%) were unmetabolized -hexadecane. The remainder of the radioactivity was found as phospholipids, free fatty acids, triglycerides, and sterol esters. Essentially no radioactivity was found in the water-soluble or residue fractions. One or three months after injection, radioactivity still was detected only in the fat-soluble fractions of the various organs, but 80-98% of the detected radioactivity was found in non-hydrocarbon lipids. 

Cortisol is an important component of the body s response to physical and psychological stress. Nervous signals regarding stress are transmitted to the hypothalamus and the release of CRH is stimulated. The resulting increase in cortisol increases levels of glucose, free fatty acids, and amino acids in the blood, providing the metabolic fuels that enable the individual to cope with the stress. A potent inhibitor of this system is cortisol itself. This hormone exerts a negative-feedback effect on the hypothalamus and the adenohypophysis and inhibits the secretion of CRH and ACTH, respectively. 

Under physiologic conditions, the balance of membrane lipid metabolism, particularly that of arachidonoyl and docosahexaenoyl chains, favors a very small and tightly controlled cellular pool of free arachidonic acid (AA, 20 4n-3) and docosahexaenoic acid (DHA, 22 6n-3), but levels increase very rapidly upon cell activation, cerebral ischemia, seizures and other types of brain trauma [1, 2], Other free fatty acids (FFAs) in addition to AA, released during cell activation and the initial stages of focal and global cerebral ischemia, are stearic acid (18 0), palmitic acid (16 0) and oleic acid (18 1). 

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