Regulation of Fatty Acid Synthase

Bennett MK, Lopez JM, Sanchez HB, Osborne TF. Sterol regulation of fatty acid synthase promoter. Coordinate feedback regulation of two major lipid pathways. J Biol Chem 1995 270 25578-25583. 

C. F. Semenkovich. 1997. Regulation of fatty acid synthase (FAS) Prog. Lipid Res. 36 43-53. (PubMed)... 

Wolf, G. 1996, Nutritional and hormonal regulation of fatty acid synthase. Nutr. Rev. 54 122-123. 

Fukuda, FI., Iritani, N., Sugimoto, T. and Ikeda, H., Transcriptional regulation of fatty acid synthase gene by insuhn/glucose, polyunsaturated fatty acid and leptin in hepatocytes and adipocytes in normal and genetically obese rats, Eur J Biochem 260 (1999) 505-511. 

Magana, M. M. and Osborne, T. F., Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter, J Biol Chem 271 (1996) 32689-32694. 

Griffin, M.J., Sul, H.S. 2004. Insulin regulation of fatty acid synthase gene transcription roles of USF and SREBP-lc. lUBMB Life 56 595-600. 

Morris, SM, Jr., Nilson, JH, Jenik, RA, Winberry, LK, McDevitt, MA, and Goodridge, AG, Molecular cloning of gene sequences for avian fatty acid synthase and evidence for nutritional regulation of fatty acid synthase mrna concentration, J Biol Chem, 1982. 257(6) 3225-3229. 

Duncan RE, Archer MC (2008) Famesol decreases serum triglycerides in rats identification of mechanisms including up-regulation of PPARalpha and down-regulation of fatty acid synthase in hepatocytes. Lipids 43(7) 619-627... 

Before closing we should point out that, over an extended period, dietary conditions can alter the levels of enzymes involved in fatty acid metabolism. For example, the concentrations of fatty acid synthase and acetyl-CoA carboxylase in rat liver are reduced four- to fivefold after fasting. When a rat is fed a fat-free diet, the concentration of fatty acid synthase is 14-fold higher than in a rat maintained on standard rat chow diet. Current evidence indicates that the levels of these enzymes are governed by the rate of enzyme synthesis, not degradation. It appears that synthesis of the enzyme, in turn, is controlled by the rate of transcription of DNA into mRNA. A question of current interest is how this transcription of DNA is regulated. 

Another major lipogenic enzyme, fatty acid synthase, is also regulated in the liver by nutritional status, insulin, glucagon and T3. Wilson et al. [78] have found that stimulation of fatty acid synthase requires both thyroid hormones and insulin (40-fold stimulation), whereas T3 or insulin alone had much smaller effects (2.5.-fold). Experiments performed in the presence or the absence of puromycin suggest that a common T3-induced peptide intermediate regulates the level of both fatty acid synthase and malic enzyme mRNAs. 

Nakamura MT, Cho HP, Clarke SD. Regulation of hepatic delta-6 desaturase expression and its role in the polyunsaturated fatty acid inhibition of fatty acid synthase gene expression in mice. J Nutr 2000 30 1561-1565. 

Graner, E., Tang, D., Rossi, S., Baron, A., Migita, T., Weinstein, L. J., Lechpammer, M., Huesken, D., Zimmermann, J., Signoretti, S. and Loda, M., The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer, Cancer Cell 5 (2004) 253-261. 

Sohby C. Regulation of fatty acid synthetase activity. J Biol Chem 1979 254 8561-8566. ElhusseinSA, MiemykJA, OhlroggeJB. Plant holo-(acyl carrier protein) synthase. Biixzhem J 1988 252 39-45. 

Jackowski . and Rock C.O., 1987. Acetoacetyl-acylcarrier protein synthase, a potential regulator of fatty acid biosynthesis in bacteria. J.Biol. Chem. 262, 7927-7931. 

In genetically normal people, fasting results in a reduction of fatty acid synthase activity with loss of the coenzyme of ACP, which thus achieves the desired objective of a shift away from fatty acid synthesis, towards breakdown. This interconversion of apo-ACP and holo-ACP is thus a very important process for the short-term regulation of fatty acid synthesis. 

Goodridge AG. Regulation of the gene for fatty acid synthase. Fed Proc 45 2399-2405, 1986. 

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