title: Upregulation of fatty acyl-CoA thioesterases in the heart and skeletal muscle of rats fed a high-fat diet.
abstract: In rodent models of diet-induced obesity, prolonged high-fat feeding increases the cellular uptake of fatty acids and causes lipotoxicity in the heart and skeletal muscle, where substrate overload to beta-oxidation generates mitochondrial stress. We examined the hypothesis that, because of its catalytic properties, acyl-CoA thioesterase (ACOT) would counteract these detrimental situations by modulating intracellular acyl-CoA levels. Rats were fed a low- or high-fat diet for up to 20 weeks, and the expressions of ACOT isoforms and fatty acid beta-oxidation enzymes were analyzed by western blotting. The expressions of ACOT1, ACOT2 and ACOT7 proteins in the heart and soleus muscle were significantly increased, by 2.0-7.6-fold, in rats fed the high-fat diet as compared with the low-fat diet group. These effects were accompanied by increases in carnitine palmitoyltransferase and acyl-CoA oxidase expression. However, ACOT was not induced in the extensor digitorum longus muscle or the liver. Subcellular fractionation of heart and soleus muscle homogenates confirmed expression of both the cytosolic and mitochondrial ACOT isoforms. These results underscore the functional relationship between ACOT and fatty acid oxidation, and suggest adaptive upregulation of ACOT to protect against fatty acid oversupply in the heart and skeletal muscle.
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192–0392, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Fujita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Momose
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohtomo
authors.forename: Azusa
authors.initials: A
authors.lastname: Nishinosono
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tanonaka
authors.forename: Hiroo
authors.initials: H
authors.lastname: Toyoda
authors.forename: Masako
authors.initials: M
authors.lastname: Morikawa
authors.forename: Junji
authors.initials: J
authors.lastname: Yamada
mesh_terms: D052436:Adipose Tissue, White; D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006321:Heart; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D010170:Palmitoyl-CoA Hydrolase / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D015430:Weight Gain
chemical_list: D004041:Dietary Fats; D010170:Palmitoyl-CoA Hydrolase