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Journal of Lipid Research, Vol. 47, 2444-2450, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

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

Gouri Ranganathan^1,*,, Resat Unal^*,, Irina Pokrovskaya^*,, Aiwei Yao-Borengasser^*,, Bounleut Phanavanh^*,, Beata Lecka-Czernik^*,, Neda Rasouli^*, and Philip A. Kern^*,

^* Central Arkansas Veterans HealthCare System, University of Arkansas for Medical Sciences, Little Rock, AR 72205
Department of Medicine, Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock, AR 72205
Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205

Published, JLR Papers in Press, August 7, 2006.

¹ To whom correspondence should be addressed. e-mail: ranganathangouri{at}uams.edu

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 (S_I). DGAT1 and FAS (but not LPL) expression were strongly correlated with S_I. 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.

Supplementary key words diacylglycerol transferase • fatty acid synthetase • lipoprotein lipase • thiazolidinedione

Abbreviations: BMI, body mass index; DGAT, acyl-coenzyme A:diacylglycerol transferase; FAS, fatty acid synthetase; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; S_I, insulin sensitivity; TZD, thiazolidinedione; WAT, white adipose tissue

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