title: Expression of DGAT2 in white adipose tissue is regulated by central leptin action.
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.
authors.affiliation: Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoyama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohsugi
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kamei
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Nemoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inoue
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ito
authors.forename: Shoko
authors.initials: S
authors.lastname: Uchida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Naoto
authors.initials: N
authors.lastname: Kubota
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terauchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D041721:3T3-L1 Cells; D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics*; D017667:Adipocytes / Q000473:pathology / Q000502:physiology; D000273:Adipose Tissue / Q000473:pathology / Q000502:physiology*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D051048:Diacylglycerol O-Acyltransferase; D004041:Dietary Fats / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006984:Hypertrophy; D007276:Injections, Intraventricular; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D010750:Phosphoproteins / Q000235:genetics*; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D020738:Leptin; D010750:Phosphoproteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D000217:Acyltransferases; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase