C75, a Fatty Acid Synthase (FAS) Inhibitor

Miguel      Lopez; Carlos      Dieguez

doi:10.2174/187221407779814615

Abstract

Recent data has demonstrated that fatty acid metabolism plays a critical role in the hypothalamic regulation of food intake and the evidence is as follows. Circulating long chain fatty acids act as nutrient surplus signals in the hypothalamus. On addition, fatty acid synthesis pathway enzymes, such as fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) and its upstream regulator, AMP-activated protein kinase (AMPK) are regulated by nutritional and hormonal stimuli. Very importantly, current evidence also indicates that fatty acid metabolism pathway may be a potential target for obesity treatment. In this sense, it has been demonstrated that pharmacological inhibition of FAS results in profound decrease in food intake and body weight in rodents. These anorectic actions are mediated by the modulation of hypothalamic neuropeptide systems, through a malonyl-CoA dependent mechanism. In this review, we recapitulate what is known about hypothalamic fatty acid metabolism and the regulation of feeding, with particular interest in a specific FAS inhibitor, C75, which has been recently patented as a potential drug for adipose mass reduction.

Keywords: AMP-activated protein kinase (AMPK), C75, cerulenin, fatty acid synthase (FAS), FAS inhibitors, food intake, hypothalamus, lipid sensing, tamoxifen