Fatty acids synthesis in adipose tissue

Increased synthesis of fatty acids De novo synthesis of fatty acids from acetyl CoA in adipose tissue is nearly undetectable in humans, except when refeeding a previously fasted individual. At other times, fatty acid synthesis in adipose tissue is not a major pathway (see Figure 24.5, G). Instead, most of the fatty acids added to the lipid stores of adipocytes are provided by dietary fat (in the form of chylomicrons), with a lesser amount is supplied by VLDL from the liver (see p. 229). 

Ball, EG. Regulation of fatty acid synthesis in adipose tissue. Adv. Enzyme Regl. 1967 4 3-18. 

In addition to its effect on insulin secretion, GLP-1(7 36) amide stimulates de novo fatty acid synthesis in adipose tissue (Oben etal., 1991). GLP-1(7 36) activates adenylate cyclase (Drucker et al., 1987 Conlon, 1988) this peptide probably stimulates insulin release in a similar manner to glucagon. 

The regulation of fatty acid synthesis in adipose tissue has been reviewed by Ball, with emphasis on a citrate-malate cycle that provides both extramitochondrial acetyl-CoA and part of the NADPH required for fatty acid synthesis. Further quantitative work on the pathways of glucose and acetate carbon in adipose tissue has also been reported. 

Mechanism of Fatty Acid Synthesis in Adipose Tissue... 

Until recently little information was available concerning the mechanism of long-chain fatty acid synthesis in adipose tissue. Martin et al. (1961) have isolated and partially purified a soluble enzyme system from rat epi-didymal adipose tissue that synthesizes long-chain fatty acids. When acetyl CoA, malonyl CoA, and reduced triphosphopyridine nucleotide are used as substrates, the major product of the reaction is palmitic acid. 

Feller and Feist (1957 Feller, 1954, 1958,1959) have presented evidence that rat adipose tissue can convert propionic acid as an intact 8-carbon unit into long-chain fatty acids, and have described a pathway of fatty acid synthesis in adipose tissue which differs from those described in the liver (Langdon, 1957 Wakil and Ganguly, 1959 Brady, 1958). Masoro... 

Insulin thus appears to play a major role in the regulation of the quantity of carbohydrate which is utilized for fatty acid synthesis in adipose tissue. It corrects the decreased incorporation of glucose carbon into long-chain fatty acids, which is a characteristic of adipose tissue removed from starved or alloxan diabetic rats. There appears to be a difference in the effectiveness of insulin in vitro and in vivo with regard to adipose tissue from alloxan diabetic rats. This may reflect the fact that adipose tissue removed from alloxan diabetic rats 3 hours after the injection of insulin and then incubated for an additional 3 hours has actually been subjected to the influence of insulin for 6 hours a comparison with controls incubated with insulin in vitro for 6 hours has not been made. Aside from this and the different routes by which the hormone gains access to the tissue, the possibility remains that secondary hormonal adjustments to insulin in vivo may be responsible for its greater effectiveness. 

Figure 6. Fatty acid synthesis in mammalian tissues showing the transhydrogenation cycle. Pyruvate is generated from glucose in the cytosol (upper portion of figure) and converted to fatty acids by a reaction sequence involving enzymes in the mitochondrial matrix (lower portion of figure). 1, pyruvate carboxylase 2, ATP citrate lyase 3, NADP-malate dehydrogenase. These reactions were absent in adipose tissue from ruminant animals (Hanson and Ballard, 1967).

Very Htfle data are available regarding effects of anaboHc steroid implants on the Hpid metaboHsm in growing mminants. Lipogenic enzyme activity and fatty acid synthesis in vitro were elevated in subcutaneous adipose tissue from bulls implanted with estradiol (44), which may account for the increase in fat content of carcasses reported in some studies. TBA implants have no effect on Hpogenesis in intact heifers, and only tend to reduce Hpogenic enzyme activities in ovariectomized heifers (45). 

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... 

Decreased uptake of fatty acids In fasting, lipoprotein lipase activity of adipose tissue is low. Consequently, circulating triacyl-glycerol of lipoproteins is not available for triacylglycerol synthesis in adipose tissue. 

The insulin-induced enhancement of fatty acid synthesis in nonruminant adipose and liver tissues is associated with an increase in the... 

B. After an overnight fast, fatty acids, released from adipose tissue, serve as fuel for other tissues. Carnitine is required to transport the fatty acids into mitochondria for P-oxidation. In the liver, P-oxidation supplies acetyl CoA for ketone body (acetoacetate and 3-hydroxybutyrate) synthesis. In a carnitine deficiency, blood levels of fatty acids will be elevated and ketone bodies will be low. Consequently, the body will use more glucose, so glucose levels will be decreased. 

P.H. Weinstock, S. Levak-Frank, and L. C. Hudgins, et al.. Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase, Proc. Natl. Acad. Sci. USA, 1997, 94, 10261-10266. 

Horton, J. D., Shimomura, 1., Brown, M. S., Hammer, R. E., Goldstein, J. L., and Shimano, H. Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2. J Clin Invest 101 (1998b) 2331-2339. 

Volpe, J. J. and Marasa, J. C., Hormonal regulation of fatty acid synthetase, acetyl-CoA carboxylase and fatty acid synthesis in mammahan adipose tissue and liver, Biochim Biophys Acta 380 (1975) 454 72. 

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