• J A Paniagua, J M Escandell-Morales, D Gil-Contreras, F J Berral de la Rosa, M Romero-Jimenez, A Gómez-Urbano, A Sanchez-Lopez, E Bellido, A Poyato, B Calatayud, and A J Vidal-Puig.
• Insulin Resistance, Metabolism and Adipose Tissue Unit, Maimonides Institute of Biomedical Research, University Hospital Reina Sofia, Córdoba, Spain; Endocrinology and Nutrition Services, University Hospital Reina Sofia, Cordoba, Spain. Electronic address: japaniaguag@yahoo.es.
• Nutrition. 2014 Feb 1; 30 (2): 177185177-85.

ObjectiveInsulin resistance (IR) and white adipose tissue (WAT) dysfunction frequently are associated with nonalcoholic fatty liver disease (NAFLD); however, the pathogenic mechanisms contributing to their clustering are not well defined. The aim of this study was to define some nutritional, anthropometric, metabolic, and genetic mechanisms contributing to their clustering.MethodsForty-five (20 men, 25 women) patients (age 45.7 ± 11.1 y) with recent diagnosis of NAFLD were grouped according to IR state. Energy balance was assessed using a food questionnaire and indirect calorimetry, and body composition with anthropometry and dual-energy x-ray absorptiometry. Biochemical and hormonal parameters combined with adipose tissue gene expression were determined. Microarray analysis of gene expression was performed in a subset of WAT samples from IR patients (n = 9), in the fasted state, after specific test meals (monounsaturated fatty acid [MUFA], saturated fat [SAT], and carbohydrate-rich) and after being challenged with insulin.ResultsIR patients exhibited higher trunk fat to leg fat ratio (P < 0.05) and had a higher ratio of SAT/MUFA fat intake (P < 0.05) than insulin-sensitive (IS) individuals. Deposition of fat in the trunk but not in the leg was directly related to liver enzyme levels (P < 0.05). IR patients also had lower adiponectin serum levels and leptin (LEP) mRNA expression in WAT compared with IS patients (P < 0.01 and P < 0.05, respectively). Microarray analysis after insulin challenge confirmed that insulin treatment induces the expression of PPARG gene and LEP and decreases GCGR gene (P < 0.05 for all) in WAT. No changes in these genes were observed in the postprandial state induced after the acute effect of specific diets.ConclusionsPatients exhibiting NAFLD and IR had preferential central fat deposition directly related to their serum alanine aminotransferase levels. These patients showed peripheral adipose tissue dysfunction and exhibited inappropriately low LEP biosynthesis that could be partially restored after anabolic conditions induced by insulin signaling.Copyright © 2014 Elsevier Inc. All rights reserved.

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