Effect of short-term starvation versus high-fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men

Exp Physiol. 2006 Jul;91(4):693-703. doi: 10.1113/expphysiol.2006.033399. Epub 2006 Apr 20.


It is currently believed that intramyocellular triglyceride (IMTG) accumulation and insulin resistance are a consequence of dietary fat ingestion and/or the elevated circulating lipid levels associated with chronic fat surplus. The purpose of this study was to compare the effect of short-term starvation versus low-carbohydrate (CHO)/high-fat diet on IMTG accumulation and the development of insulin resistance in physically fit men. Intramyocellular triglyceride content, measured as intramyocellular lipid (IMCL) by proton magnetic resonance spectroscopy (1H-MRS), and glucose tolerance/insulin sensitivity, assessed by frequently sampled intravenous glucose tolerance test (IVGTT), were determined after 67 h of: (a) water-only starvation (S); and (b) very low-CHO/high-fat diet (LC). These diets had in common significant restriction of CHO availability but large differences in fat content. All results were compared with those measured after a mixed CHO diet (C). Dietary interventions were administered by cross-over design. The level of dietary-induced IMTG accumulation (P = 0.46), insulin resistance (P = 0.27) and glucose intolerance (P = 0.29) was not different between S and LC treatments. Intramyocellular triglyceride content and insulin sensitivity were negatively correlated (r = -0.63, P < 0.01). Therefore, whilst insulin resistance may be due to fat accumulation at a cellular level, in the integrated human organism this outcome is not exclusively a function of dietary fat intake. The comparable level of IMTG accumulation and insulin resistance following S and LC may suggest that these metabolic perturbations are largely a consequence of the increased lipolytic response associated with CHO restriction.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology
  • Dietary Fats / metabolism*
  • Fasting / physiology*
  • Food Deprivation / physiology*
  • Humans
  • Insulin Resistance / physiology*
  • Male
  • Muscle, Skeletal / metabolism*
  • Physical Fitness / physiology*
  • Triglycerides / metabolism*


  • Dietary Fats
  • Triglycerides