title: Regulated expression of acyl-CoA thioesterases in the differentiation of cultured rat brown adipocytes.
abstract: Acyl-CoA thioesterases (ACOTs) are enzymes that catalyze the hydrolysis of fatty acyl-CoAs to free fatty acids and CoA-SH. In this study, we show that the expression profile of the ACOT isoforms changes remarkably during the differentiation of cultured rat brown adipocytes. Immunocytochemistry suggested that cytosolic ACOT1 was present in the preadipocytes, while mitochondrial ACOT2 was additionally expressed as the cells differentiated, concurrent with the accumulation of lipid droplets in the cytoplasm. Western blotting confirmed that, in contrast to ACOT1, the ACOT2 expression level was very low in the preadipocytes. However, after differentiation, the ACOT1 level fell to one-half of the baseline level and ACOT2 increased 18-fold. ACOT2 expression in the differentiated adipocytes was further enhanced by treatment with lipids or troglitazone. These changes in the ACOT2 expression level correlated well with changes in the expression of carnitine palmitoyltransferase 2, a mitochondrial β-oxidation enzyme. These results indicate that, in differentiating brown adipocytes, cytosolic ACOT1 becomes downregulated as the cellular use of acyl-CoA increases, while mitochondrial ACOT2 is upregulated as the β-oxidation capacity increases. ACOT isoform expression may be regulated during brown adipocyte differentiation to support the fat storage and combustion characteristics of this cell type.
authors.affiliation: Department of Clinical Molecular Genetics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Momose
authors.forename: Mariko
authors.initials: M
authors.lastname: Fujita
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohtomo
authors.forename: Natsumi
authors.initials: N
authors.lastname: Umemoto
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: D052437:Adipocytes, Brown / Q000166:cytology / Q000201:enzymology*; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000201:enzymology*; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D015536:Down-Regulation; D024101:Mitochondrial Proteins; D010170:Palmitoyl-CoA Hydrolase / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013869:Thiolester Hydrolases / Q000096:biosynthesis*
chemical_list: D024101:Mitochondrial Proteins; D013869:Thiolester Hydrolases; C546434:Acot2 protein, rat; D010170:Palmitoyl-CoA Hydrolase