Expression of DGAT2 in white adipose tissue is regulated by central leptin action

Ryo Suzuki, Kazuyuki Tobe, Masashi Aoyama, Kentaro Sakamoto, Mitsuru Ohsugi, Nozomu Kamei, Shigeyuki Nemoto, Atsushi Inoue, Yusuke Ito, Shoko Uchida, Kazuo Hara, Toshimasa Yamauchi, Naoto Kubota, Yasuo Terauchi, Takashi Kadowaki*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes catalyze the final step in mammalian triglyceride synthesis, and their functions are considered to be involved in the mechanisms of obesity, insulin resistance, and leptin resistance. Insulin receptor substrate-2 (IRS-2)-deficient mice exhibit obesity-associated with hypertrophic adipocytes and leptin resistance. Screening for transcripts of genes involved in fatty acid and triglyceride synthesis to investigate the mechanism of the hypertrophic change in the adipocytes showed that expression of DGAT2 mRNA was up-regulated in the white adipose tissue (WAT) of Irs2-/- mice, whereas that of DGAT1 was down-regulated. This reciprocal expression of DGAT1 and DGAT2 was also observed in WAT of leptin-deficient ob/ob mice. A high fat diet also resulted in increased DGAT2 and reduced DGAT1 in the WAT of C57BL/6 mice. Induction of adipocyte hypertrophy in vitro up-regulated both DGAT1 and DGAT2 expression in 3T3-L1 cells, suggesting that adipocyte non-autonomous mechanism in vivo is required for the reciprocal changes in expression of DGAT1 and DGAT2. In fact, intracerebroventricular infusion of leptin reduced DGAT2 expression in WAT of Irs2-/- mice and ob/ob mice, independently of DGAT1 expression. We propose the hypothesis that leptin regulates adipocyte size by altering expression patterns of DGAT via central nervous system to determine the levels of triglyceride synthesis.

Original languageEnglish
Pages (from-to)3331-3337
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number5
DOIs
StatePublished - 2005/02/04

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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