Identification of a Novel Member of the Carboxylesterase Family That Hydrolyzes Triacylglycerol

A Potential Role in Adipocyte Lipolysis

  1. Hiroaki Okazaki1,
  2. Masaki Igarashi1,
  3. Makiko Nishi1,
  4. Makiko Tajima1,
  5. Motohiro Sekiya1,
  6. Sachiko Okazaki1,
  7. Naoya Yahagi1,
  8. Ken Ohashi1,
  9. Kazuhisa Tsukamoto1,
  10. Michiyo Amemiya-Kudo2,
  11. Takashi Matsuzaka3,
  12. Hitoshi Shimano3,
  13. Nobuhiro Yamada3,
  14. Junken Aoki4,
  15. Rei Morikawa4,
  16. Yasukazu Takanezawa4,
  17. Hiroyuki Arai4,
  18. Ryozo Nagai5,
  19. Takashi Kadowaki1,
  20. Jun-ichi Osuga1 and
  21. Shun Ishibashi16
  1. 1Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  2. 2Okinaka Memorial Institute for Medical Research and Toranomon Hospital, Tokyo, Japan
  3. 3Metabolism, Endocrinology and Atherosclerosis, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan
  4. 4Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  5. 5Department of Cardiovascular Diseases, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  6. 6Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, Japan
  1. Address correspondence and reprint requests to Shun Ishibashi, Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. E-mail: ishibash{at}jichi.ac.jp

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.

Footnotes

  • H.O. and M.I. contributed equally to this work.

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted April 17, 2006.
    • Received May 6, 2005.
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  1. doi: 10.2337/db05-0585 Diabetes July 2006 vol. 55 no. 7 2091-2097
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