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.
Highlights
Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation
FAS regulates de novo lipogenesis from acetyl-CoA, Abbreviations: BMI, body mass index; DGAT, acyl-coenzyme A:diacylglycerol transferase; FAS, fatty acid synthetase; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; SI, insulin sensitivity; TZD, thiazolidinedione; WAT, white adipose tissue
To better understand the relationships between DGAT1, FAS, and LPL with SI, we examined the expression of these lipogenic enzymes in adipose tissue of NGT and IGT subjects who were matched for BMI
Summary
Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation. A number of genes are involved in adipocyte lipid accumulation, including acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL. FAS regulates de novo lipogenesis from acetyl-CoA, Abbreviations: BMI, body mass index; DGAT, acyl-coenzyme A:diacylglycerol transferase; FAS, fatty acid synthetase; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; SI, insulin sensitivity; TZD, thiazolidinedione; WAT, white adipose tissue. LPL is expressed at high levels in adipose tissue and muscle and hydrolyzes triglyceride-rich lipoproteins at the capillary endothelium to generate NEFA for uptake in peripheral tissues [17] Both FAS and LPL are increased by feeding [18,19,20,21], and systemic overexpression of LPL in rabbits results in increases in whole body SI [22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
