Document Detail

Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: a potential role in adipocyte lipolysis.
MedLine Citation:
PMID:  16804080     Owner:  NLM     Status:  MEDLINE    
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.
Hiroaki Okazaki; Masaki Igarashi; Makiko Nishi; Makiko Tajima; Motohiro Sekiya; Sachiko Okazaki; Naoya Yahagi; Ken Ohashi; Kazuhisa Tsukamoto; Michiyo Amemiya-Kudo; Takashi Matsuzaka; Hitoshi Shimano; Nobuhiro Yamada; Junken Aoki; Rei Morikawa; Yasukazu Takanezawa; Hiroyuki Arai; Ryozo Nagai; Takashi Kadowaki; Jun-Ichi Osuga; Shun Ishibashi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetes     Volume:  55     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-28     Completed Date:  2006-08-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2091-7     Citation Subset:  AIM; IM    
Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
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MeSH Terms
3T3 Cells
Adipocytes / cytology,  enzymology*
Adipose Tissue / enzymology
Amino Acid Sequence
Carboxylesterase / metabolism*
Cell Differentiation
Conserved Sequence
DNA, Complementary
Dipeptides / chemistry
Molecular Sequence Data
Sequence Alignment
Sequence Homology, Amino Acid
Substrate Specificity
Triglycerides / metabolism*
Reg. No./Substance:
0/DNA, Complementary; 0/Dipeptides; 0/Triglycerides; EC

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