TY - JOUR
T1 - Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol
T2 - A potential role in adipocyte lipolysis
AU - Okazaki, Hiroaki
AU - Igarashi, Masaki
AU - Nishi, Makiko
AU - Tajima, Makiko
AU - Sekiya, Motohiro
AU - Okazaki, Sachiko
AU - Yahagi, Naoya
AU - Ohashi, Ken
AU - Tsukamoto, Kazuhisa
AU - Amemiya-Kudo, Michiyo
AU - Matsuzaka, Takashi
AU - Shimano, Hitoshi
AU - Yamada, Nobuhiro
AU - Aoki, Junken
AU - Morikawa, Rei
AU - Takanezawa, Yasukazu
AU - Arai, Hiroyuki
AU - Nagai, Ryozo
AU - Kadowaki, Takashi
AU - Osuga, Jun Ichi
AU - Ishibashi, Shun
PY - 2006/7
Y1 - 2006/7
N2 - Molecular mechanisms underlying lipolysis, as defined by mobilization of fatty acids from adipose tissue, are not fully understood. A database search for enzymes with α/β 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.
AB - Molecular mechanisms underlying lipolysis, as defined by mobilization of fatty acids from adipose tissue, are not fully understood. A database search for enzymes with α/β 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.
KW - ATGL, adipose triglyceride lipase
KW - BAT, brown adipose tissue
KW - DMEM, Dulbecco's modified Eagle's medium
KW - FFA, free fatty acid
KW - HSL, hormone-sensitive lipase
KW - PNPB, p-nitrophenyl butyrate
KW - iPLA2, Ca-independent PLA2
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UR - http://www.scopus.com/inward/citedby.url?scp=33747072385&partnerID=8YFLogxK
U2 - 10.2337/db05-0585
DO - 10.2337/db05-0585
M3 - Article
C2 - 16804080
AN - SCOPUS:33747072385
VL - 55
SP - 2091
EP - 2097
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -