The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: Effects of obesity, insulin resistance, and TZD treatment

Gouri Ranganathan, Resat Unal, Irina Pokrovskaya, Aiwei Yao-Borengasser, Bounleut Phanavanh, Beata Lecka-Czernik, Neda Rasouli, Philip A. Kern

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation. To study the relationship of DGAT1, FAS, and LPL with insulin, we examined adipose mRNA expression of these genes in subjects with a wide range of insulin sensitivity (SI). DGAT1 and FAS (but not LPL) expression were strongly correlated with SI. In addition, the expression of DGAT1 and FAS (but not LPL) were higher in normal glucose-tolerant subjects compared with subjects with impaired glucose tolerance (IGT) (P < 0.005). To study the effects of insulin sensitizers, subjects with IGT were treated with pioglitazone or metformin for 10 weeks, and lipogenic enzymes were measured in adipose tissue. After pioglitazone treatment, DGAT1 expression was increased by 33 ± 10% (P < 0.05) and FAS expression increased by 63 ± 8% (P < 0.05); however, LPL expression was not altered. DGAT1, FAS, and LPL mRNA expression were not significantly changed after metformin treatment. The treatment of mice with rosiglitazone also resulted in an increase in adipose expression of DGAT1 by 2- to 3-fold, as did the treatment of 3T3 F442A adipocytes in vitro with thiazolidinediones. These data support a more global concept suggesting that adipose lipid storage functions to prevent peripheral lipotoxicity.

Original languageEnglish
Pages (from-to)2444-2450
Number of pages7
JournalJournal of Lipid Research
Volume47
Issue number11
DOIs
StatePublished - Nov 2006

Keywords

  • Diacylglycerol transferase
  • Fatty acid synthetase
  • Lipoprotein lipase
  • Thiazolidinedione

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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