title: Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis.
abstract: Molecular mechanisms underlying lipolysis, as defined by mobilization of fatty acids from adipose tissue, are not fully understood. A database search for enzymes with alpha/beta hydrolase folds, the GXSXG motif for serine esterase and the His-Gly dipeptide motif, has provided a previously unannotated gene that is induced during 3T3-L1 adipocytic differentiation. Because of its remarkable structural resemblance to triacylglycerol hydrolase (TGH) with 70.4% identity, we have tentatively designated this enzyme as TGH-2 and the original TGH as TGH-1. TGH-2 is also similar to TGH-1 in terms of tissue distribution, subcellular localization, substrate specificity, and regulation. Both enzymes are predominantly expressed in liver, adipose tissue, and kidney. In adipocytes, they are localized in microsome and fatcake. Both enzymes hydrolyzed p-nitophenyl butyrate, triolein, and monoolein but not diolein, cholesteryl oleate, or phospholipids; hydrolysis of short-chain fatty acid ester was 30,000-fold more efficient than that of long-chain fatty acid triacylglycerol. Fasting increased the expression of both genes in white adipose tissue, whereas refeeding suppressed their expression. RNA silencing of TGH-2 reduced isoproterenol-stimulated glycerol release by 10% in 3T3-L1 adipocytes, while its overexpression increased the glycerol release by 20%. Thus, TGH-2 may make a contribution to adipocyte lipolysis during period of increased energy demand.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. ishibash@jichi.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
authors.forename: Masaki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Makiko
authors.initials: M
authors.lastname: Nishi
authors.forename: Makiko
authors.initials: M
authors.lastname: Tajima
authors.forename: Motohiro
authors.initials: M
authors.lastname: Sekiya
authors.forename: Sachiko
authors.initials: S
authors.lastname: Okazaki
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Michiyo
authors.initials: M
authors.lastname: Amemiya-Kudo
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuzaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Rei
authors.initials: R
authors.lastname: Morikawa
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Takanezawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000201:enzymology*; D000273:Adipose Tissue / Q000201:enzymology; D000595:Amino Acid Sequence; D000818:Animals; D043182:Carboxylesterase / Q000378:metabolism*; D002454:Cell Differentiation; D017124:Conserved Sequence; D018076:DNA, Complementary; D004151:Dipeptides / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D008066:Lipolysis; D051379:Mice; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D004151:Dipeptides; D014280:Triglycerides; D043182:Carboxylesterase