PMID:21389266

Citation	Wu, M, Singh, SB, Wang, J, Chung, CC, Salituro, G, Karanam, BV, Lee, SH, Powles, M, Ellsworth, KP, Lassman, ME, Miller, C, Myers, RW, Tota, MR, Zhang, BB and Li, C (2011) Antidiabetic and antisteatotic effects of the selective fatty acid synthase (FAS) inhibitor platensimycin in mouse models of diabetes. Proc. Natl. Acad. Sci. U.S.A. 108:5378-83
Abstract	Platensimycin (PTM) is a recently discovered broad-spectrum antibiotic produced by Streptomyces platensis. It acts by selectively inhibiting the elongation-condensing enzyme FabF of the fatty acid biosynthesis pathway in bacteria. We report here that PTM is also a potent and highly selective inhibitor of mammalian fatty acid synthase. In contrast to two agents, C75 and cerulenin, that are widely used as inhibitors of mammalian fatty acid synthase, platensimycin specifically inhibits fatty acid synthesis but not sterol synthesis in rat primary hepatocytes. PTM preferentially concentrates in liver when administered orally to mice and potently inhibits hepatic de novo lipogenesis, reduces fatty acid oxidation, and increases glucose oxidation. Chronic administration of platensimycin led to a net reduction in liver triglyceride levels and improved insulin sensitivity in db/+ mice fed a high-fructose diet. PTM also reduced ambient glucose levels in db/db mice. These results provide pharmacological proof of concept of inhibiting fatty acid synthase for the treatment of diabetes and related metabolic disorders in animal models.
Links	PubMed PMC3069196 Online version:10.1073/pnas.1002588108
Keywords	Adamantane/therapeutic use; Aminobenzoic Acids/therapeutic use; Anilides/therapeutic use; Animals; Anti-Infective Agents/therapeutic use; Diabetes Mellitus/drug therapy; Disease Models, Animal; Fatty Acid Synthetase Complex/antagonists & inhibitors; Fatty Acids/biosynthesis; Fatty Liver/drug therapy; Glucose/metabolism; Humans; Hypoglycemic Agents/therapeutic use; Liver/metabolism; Mice; Mice, Mutant Strains; Oxidation-Reduction; Sterols/biosynthesis
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:FAS		GO:0004312: fatty acid synthase activity	ECO:0000314:		F		Figure 1	complete CACAO 4315
RAT:FAS	enables	GO:0004312: fatty acid synthase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete

References

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