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A more recent version of this article appeared on November 1, 2006

Papers In Press, published online ahead of print August 7, 2006
J. Lipid Res., doi:10.1194/jlr.M600248-JLR200
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Submitted on June 7, 2006
Revised on July 27, 2006
Accepted on August 7, 2006

The lipogenic enzymes DGAT1, fatty acid synthetase, and lipoprotein lipase in adipose tissue: Effects of obesity, insulin resistance, and treatment with thiazolidinediones

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

Internal medicine, University of Arkansas for medical Science, Little Rock, Arkansas 72205

Corresponding Author: Ranganathangouri{at}uams.edu

Acyl CoA: diacylglycerol transferase (DGAT), fatty acid synthetase (FAS) and lipoprotein lipase (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 (NGT) subjects as compared to IGT subjects (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. Following 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 following metformin treatment. The treatment of mice with rosiglitazone also resulted in an increase in adipose expression of DGAT1 by 2-3 fold, as did the treatment of 3T3 F442A adipocytes in vitro with TZDs. These data support a more global concept suggesting that adipose lipid storage functions to prevent peripheral lipotoxicity.


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