Identification of a novel member of the carboxylesterase family that hydrolyzes triacylglycerol: A potential role in adipocyte lipolysis

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 OsugaShun Ishibashi

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)2091-2097
Number of pages7
JournalDiabetes
Volume55
Issue number7
DOIs
Publication statusPublished - 2006 Jul

Keywords

  • ATGL, adipose triglyceride lipase
  • BAT, brown adipose tissue
  • DMEM, Dulbecco's modified Eagle's medium
  • FFA, free fatty acid
  • HSL, hormone-sensitive lipase
  • PNPB, p-nitrophenyl butyrate
  • iPLA2, Ca-independent PLA2

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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