Gender dimorphism in high-fat-diet-induced insulin resistance in skeletal muscle of aged rats

Cell Physiol Biochem. 2008;22(5-6):539-48. doi: 10.1159/000185538. Epub 2008 Dec 9.


Muscle resistance to insulin plays a key role in the metabolic dysregulation associated to obesity. A pro-inflammatory and pro-oxidant status has been proposed to be the link between dietary obesity and insulin resistance. Given the gender differences previously found in mitochondrial function and oxidative stress, the aim of the present study was to investigate whether this gender dimorphism leads to differences in the development of high-fat-diet-induced insulin resistance in rat skeletal muscle. Male and female rats of 15 months of age were fed with a high-fat-diet (32% fat) for 14 weeks. Control male rats showed a more marked insulin resistance status compared to females, as indicated by the glucose tolerance curve profile and the serum insulin, resistin and adiponectin levels. High-fat-diet feeding induced an excess of body weight of 16.2% in males and 38.4% in females, an increase in both muscle mitochondrial hydrogen peroxide production and in oxidative damage, together with a decrease in the Mn-superoxide dismutase activity in both genders. However, high-fat-diet fed female rats showed a less marked insulin resistance profile than males, higher mitochondrial oxygen consumption and cytochrome c oxidase activity, and a better capacity to counteract the oxidative-stress-dependent insulin resistance through an overexpression of both muscle UCP3 and GLUT4 proteins. These results point to a gender dimorphism in the insulin resistance status and in the response of skeletal muscle to high-fat-diet feeding which could be related to a more detrimental effect of age in male rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood
  • Aging / drug effects*
  • Aging / physiology*
  • Animals
  • Antioxidants / metabolism
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Dietary Fats / pharmacology*
  • Electron Transport Complex IV / metabolism
  • Energy Metabolism / drug effects
  • Female
  • Glucose Tolerance Test
  • Glucose Transporter Type 4 / metabolism
  • Hydrogen Peroxide / metabolism
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Ion Channels / metabolism
  • Lipid Peroxides / metabolism
  • Male
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Mitochondrial Proteins / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / physiology*
  • Oxygen Consumption / drug effects
  • Protein Carbonylation / drug effects
  • Rats
  • Rats, Wistar
  • Sex Characteristics*
  • Uncoupling Protein 3
  • Weight Gain / drug effects


  • Adipokines
  • Antioxidants
  • Blood Glucose
  • Dietary Fats
  • Glucose Transporter Type 4
  • Insulin
  • Ion Channels
  • Lipid Peroxides
  • Mitochondrial Proteins
  • Ucp3 protein, rat
  • Uncoupling Protein 3
  • Hydrogen Peroxide
  • Electron Transport Complex IV