Increased subcutaneous adipose tissue expression of genes involved in glycerolipid-fatty acid cycling in obese insulin-resistant versus -sensitive individuals.

Autor:	Gauthier MS; Institut de recherches cliniques de Montréal (M.-S.G., J.R.P., M.-E.L., B.C., R.R.-L.), Montréal, QC H2W 1R7, Canada; Montreal Diabetes Research Center at the Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) (M.-S.G., M.-E.L., R.S., S.R.M.M., M.P., R.R.-L.), Montréal, QC H2X 0A9, Canada; McGill University and Centre d'Innovation Génome Québec (R.S.), Montréal, QC H3A 0G1, Canada; Molecular Nutrition Unit at the CRCHUM (S.R.M.M., M.P.), Montréal, QC H2X 0A9, Canada; Diabetes and Metabolism Research Unit (N.B.R.), and Department of Medicine and Section of Endocrinology (N.B.R.), Boston University School of Medicine, Boston, Massachusetts 02118; Departments of Biochemistry (B.C., M.P.) and Nutrition (M.-E.L., M.P., R.R.-L.), Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3J7, Canada., Pérusse JR, Lavoie MÈ, Sladek R, Madiraju SR, Ruderman NB, Coulombe B, Prentki M, Rabasa-Lhoret R
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2014 Dec; Vol. 99 (12), pp. E2518-28.
DOI:	10.1210/jc.2014-1662
Abstrakt:	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.
Databáze:	MEDLINE
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