Central obesity and altered peripheral adipose tissue gene expression characterize the NAFLD patient with insulin resistance: Role of nutrition and insulin challenge

Nutrition. 2014 Feb;30(2):177-85. doi: 10.1016/j.nut.2013.07.017.


Objective: Insulin 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.

Methods: Forty-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.

Results: IR 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.

Conclusions: Patients 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.

Keywords: Adipokines and leptin; Adipose tissue dysfunction; Insulin resistance; Nonalcoholic fatty liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adiponectin / blood
  • Adipose Tissue, White / metabolism*
  • Adult
  • Body Composition
  • Body Mass Index
  • Cross-Over Studies
  • Dietary Carbohydrates / administration & dosage
  • Energy Metabolism
  • Fatty Acids / administration & dosage
  • Fatty Acids, Monounsaturated / administration & dosage
  • Fatty Liver / diet therapy
  • Fatty Liver / genetics*
  • Feeding Behavior*
  • Female
  • Gene Expression*
  • Humans
  • Insulin / blood
  • Insulin Resistance / genetics*
  • Interleukin-6 / blood
  • Leptin / blood
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Nutritional Status
  • Obesity, Abdominal / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Randomized Controlled Trials as Topic
  • Surveys and Questionnaires
  • Tumor Necrosis Factor-alpha / blood


  • Adiponectin
  • Dietary Carbohydrates
  • Fatty Acids
  • Fatty Acids, Monounsaturated
  • Insulin
  • Interleukin-6
  • Leptin
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha