Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis.
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.
Okazaki
Hiroaki
H
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. ishibash@jichi.ac.jp
Igarashi
Masaki
M
Nishi
Makiko
M
Tajima
Makiko
M
Sekiya
Motohiro
M
Okazaki
Sachiko
S
Yahagi
Naoya
N
Ohashi
Ken
K
Tsukamoto
Kazuhisa
K
Amemiya-Kudo
Michiyo
M
Matsuzaka
Takashi
T
Shimano
Hitoshi
H
Yamada
Nobuhiro
N
Aoki
Junken
J
Morikawa
Rei
R
Takanezawa
Yasukazu
Y
Arai
Hiroyuki
H
Nagai
Ryozo
R
Kadowaki
Takashi
T
Osuga
Jun-Ichi
J
Ishibashi
Shun
S
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*
D018076:DNA, Complementary; D004151:Dipeptides; D014280:Triglycerides; D043182:Carboxylesterase