Increased Subcutaneous Adipose Tissue Expression of Genes Involved in Glycerolipid-Fatty Acid Cycling in Obese Insulin-Resistant Versus -Sensitive Individuals

• Published in: The journal of clinical endocrinology and metabolism Vol. 99; no. 12; pp. E2518 - E2528
• Main Authors: Gauthier, Marie-Soleil, Pérusse, Joelle R., Lavoie, Marie-Ève, Sladek, Robert, Madiraju, S. R. Murthy, Ruderman, Neil B., Coulombe, Benoit, Prentki, Marc, Rabasa-Lhoret, Rémi
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.12.2014; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Adipose tissue; Aged; Biopsy; Body fat; Body mass index; Body weight loss; Cohort Studies; Cross-Sectional Studies; Diet, Reducing; Fatty acids; Fatty Acids - genetics; Fatty Acids - metabolism; Female; Gene Expression; Glucose tolerance; Glycolipids - genetics; Glycolipids - metabolism; Hot Topics in Translational Endocrinology; Humans; Hypocaloric diet; Insulin resistance; Insulin Resistance - genetics; Lipolysis; Longitudinal Studies; Mass spectroscopy; Metabolism; Middle Aged; mRNA; Obesity; Obesity - diet therapy; Obesity - genetics; Obesity - metabolism; Postmenopause - genetics; Protein biosynthesis; Subcutaneous Fat - metabolism; Transcription; Weight control
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2014-1662

Context:A subpopulation of obese individuals remains insulin sensitive (ISO). They represent a unique human model to investigate factors underlying insulin resistance (IR) without the confounding effect of major differences in weight/adiposity. Altered fatty-acid (FA) metabolism in sc adipose tissue (SAT) contributes to obesity-associated IR.Objective:To test the hypothesis that ISO and body mass index-matched insulin-resistant obese (IRO) patients demonstrate differential SAT expression profiles of genes involved in glycerolipid-FA metabolism and that weight loss-induced improvement of IR ameliorates these changes.Design and Setting:A cross-sectional and longitudinal study.Patients and Intervention:Thirty-eight nondiabetic obese women were stratified into ISO (n = 25) or IRO (n = 13) groups based on hyperinsulinemic-euglycemic clamp results. Subjects were studied before and after a 6-month hypocaloric diet intervention.Main Outcome Measures:mRNA (quantitative RT-PCR) and protein (mass spectrometry and immunoblots) levels were measured in SAT biopsies.Results:Despite having age, body mass index, and fat mass similar to ISO individuals, IRO patients had lower insulin sensitivity and glucose tolerance (P < .05). Baseline SAT mRNA and protein levels of genes involved in both the synthesis and lipolysis of glycerolipid-FAs were higher in IRO individuals (P < .05), even when groups were matched for visceral adipose tissue content. The dietary intervention resulted in approximately 6% weight loss in both the IRO and ISO groups (P < .05) but only ameliorated insulin sensitivity in IRO individuals (P < .05). Likewise, the intervention reduced the expression of most glycerolipid-FA metabolism genes (P < .05), with expression levels in IRO individuals being restored to ISO levels.Conclusions:Increased SAT expression of genes involved in both the synthesis and hydrolysis of glycerolipid-FAs is closely associated with IR in obese women. The results suggest that enhanced glycerolipid-FA cycling in SAT contributes to obesity-associated IR.