High-fat diet decreases energy expenditure and expression of genes controlling lipid metabolism, mitochondrial function and skeletal system development in the adipose tissue, along with increased expression of extracellular matrix remodelling- and inflammation-related genes

Br J Nutr. 2015 Mar 28;113(6):867-77. doi: 10.1017/S0007114515000100. Epub 2015 Mar 6.

Abstract

The aim of the present study was to identify the genes differentially expressed in the visceral adipose tissue in a well-characterised mouse model of high-fat diet (HFD)-induced obesity. Male C57BL/6J mice (n 20) were fed either HFD (189 % of energy from fat) or low-fat diet (LFD, 42 % of energy from fat) for 16 weeks. HFD-fed mice exhibited obesity, insulin resistance, dyslipidaemia and adipose collagen accumulation, along with higher levels of plasma leptin, resistin and plasminogen activator inhibitor type 1, although there were no significant differences in plasma cytokine levels. Energy intake was similar in the two diet groups owing to lower food intake in the HFD group; however, energy expenditure was also lower in the HFD group than in the LFD group. Microarray analysis revealed that genes related to lipolysis, fatty acid metabolism, mitochondrial energy transduction, oxidation-reduction, insulin sensitivity and skeletal system development were down-regulated in HFD-fed mice, and genes associated with extracellular matrix (ECM) components, ECM remodelling and inflammation were up-regulated. The top ten up- or down-regulated genes include Acsm3, mt-Nd6, Fam13a, Cyp2e1, Rgs1 and Gpnmb, whose roles in the deterioration of obesity-associated adipose tissue are poorly understood. In conclusion, the genes identified here provide new therapeutic opportunities for prevention and treatment of diet-induced obesity.

Keywords: Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, White / immunology
  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / pathology
  • Adiposity
  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Coenzyme A Ligases / genetics
  • Coenzyme A Ligases / metabolism*
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Diet, High-Fat / adverse effects
  • Energy Metabolism
  • Extracellular Matrix / immunology
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Expression Regulation, Enzymologic*
  • Insulin Resistance
  • Male
  • Mice, Inbred C57BL
  • Mitochondria / enzymology
  • Mitochondria / immunology
  • Mitochondria / metabolism
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / metabolism
  • NADH Dehydrogenase / genetics
  • NADH Dehydrogenase / metabolism*
  • Obesity / etiology
  • Obesity / immunology
  • Obesity / metabolism*
  • Obesity / pathology

Substances

  • Biomarkers
  • GTPase-Activating Proteins
  • Cytochrome P-450 CYP2E1
  • NADH Dehydrogenase
  • Coenzyme A Ligases