Enhanced lipid oxidation and maintenance of muscle insulin sensitivity despite glucose intolerance in a diet-induced obesity mouse model

PLoS One. 2013 Aug 12;8(8):e71747. doi: 10.1371/journal.pone.0071747. eCollection 2013.


Background: Diet-induced obesity is a rising health concern which can lead to the development of glucose intolerance and muscle insulin resistance and, ultimately, type II diabetes mellitus. This research investigates the associations between glucose intolerance or muscle insulin resistance and tissue specific changes during the progression of diet-induced obesity.

Methodology: C57BL/6J mice were fed a normal or high-fat diet (HFD; 60% kcal fat) for 3 or 8 weeks. Disease progression was monitored by measurements of body/tissue mass changes, glucose and insulin tolerance tests, and ex vivo glucose uptake in intact muscles. Lipid metabolism was analyzed using metabolic chambers and ex vivo palmitate assays in intact muscles. Skeletal muscle, liver and adipose tissues were analyzed for changes in inflammatory gene expression. Plasma was analyzed for insulin levels and inflammatory proteins. Histological techniques were used on muscle and liver cryosections to assess metabolic and morphological changes.

Principal findings/conclusions: A rapid shift in whole body metabolism towards lipids was observed with HFD. Following 3 weeks of HFD, elevated total lipid oxidation and an oxidative fiber type shift had occurred in the skeletal muscle, which we propose was responsible for delaying intramyocellular lipid accumulation and maintaining muscle's insulin sensitivity. Glucose intolerance was present after three weeks of HFD and was associated with an enlarged adipose tissue depot, adipose tissue inflammation and excess hepatic lipids, but not hepatic inflammation. Furthermore, HFD did not significantly increase systemic or muscle inflammation after 3 or 8 weeks of HFD suggesting that early diet-induced obesity does not cause inflammation throughout the whole body. Overall these findings indicate skeletal muscle did not contribute to the development of HFD-induced impairments in whole-body glucose tolerance following 3 weeks of HFD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Body Composition
  • Body Weight
  • Diet, High-Fat / adverse effects*
  • Disease Models, Animal
  • Glucose Intolerance / metabolism*
  • Insulin Resistance*
  • Lipid Metabolism*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Muscle, Skeletal / metabolism*
  • Obesity / etiology*
  • Obesity / metabolism*
  • Oxidation-Reduction
  • Panniculitis / genetics
  • Panniculitis / metabolism
  • Panniculitis / pathology
  • Signal Transduction
  • Time Factors

Grant support

This work was funded by grants to TJH from the Natural Sciences and Engineering Research Council of Canada and the Canadian Foundation for Innovation/Ontario Ministry of Research Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.