Fatty acid synthase gene regulation in primary hypothalamic neurons.
Understanding the mechanisms that regulate feeding is critical to the development of therapeutic interventions for obesity. Many studies indicate that enzymes within fatty acid metabolic pathways may serve as targets for pharmacological tools to treat this epidemic. We, and others have previously demonstrated that C75, a fatty acid synthase (FAS) inhibitor, induced significant anorexia and weight loss by both central and peripheral mechanisms. Because the hypothalamus is important in the regulation of homeostatic processes for feeding control, we have identified pathways that alter the gene expression of FAS in primary hypothalamic neuronal cultures. Insulin, glucose and AICAR (an activator of AMP-activated protein kinase) affected changes in hypothalamic FAS mRNA, which may be regulated via the SREBP1c dependent or independent pathway.
Kim
Eun-Kyoung
EK
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. kimeunk@msu.edu
Kleman
Amy M
AM
Ronnett
Gabriele V
GV
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D064429:Fatty Acid Synthases / Q000235:genetics*; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000196:embryology / Q000201:enzymology* / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D013997:Time Factors
D007328:Insulin; D020033:Protein Isoforms; D012333:RNA, Messenger; D012265:Ribonucleotides; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D000620:Aminoimidazole Carboxamide; D064429:Fatty Acid Synthases; C031143:AICA ribonucleotide; D005947:Glucose
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