Heat treatment improves glucose tolerance and prevents skeletal muscle insulin resistance in rats fed a high-fat diet

Diabetes. 2009 Mar;58(3):567-78. doi: 10.2337/db08-1070. Epub 2008 Dec 10.


Objective: Heat treatment and overexpression of heat shock protein 72 (HSP72) have been shown to protect against high-fat diet-induced insulin resistance, but little is known about the underlying mechanism or the target tissue of HSP action. The purpose of this study is to determine whether in vivo heat treatment can prevent skeletal muscle insulin resistance.

Research design and methods: Male Wistar rats were fed a high-fat diet (60% calories from fat) for 12 weeks and received a lower-body heat treatment (41 degrees C for 20 min) once per week.

Results: Our results show that heat treatment shifts the metabolic characteristics of rats on a high-fat diet toward those on a standard diet. Heat treatment improved glucose tolerance, restored insulin-stimulated glucose transport, and increased insulin signaling in soleus and extensor digitorum longus (EDL) muscles from rats fed a high-fat diet. Heat treatment resulted in decreased activation of Jun NH2-terminal kinase (JNK) and inhibitor of kappaB kinase (IKK-beta), stress kinases implicated in insulin resistance, and upregulation of HSP72 and HSP25, proteins previously shown to inhibit JNK and IKK-beta activation, respectively. Mitochondrial citrate synthase and cytochrome oxidase activity decreased slightly with the high-fat diet, but heat treatment restored these activities. Data from L6 cells suggest that one bout of heat treatment increases mitochondrial oxygen consumption and fatty acid oxidation.

Conclusions: Our results indicate that heat treatment protects skeletal muscle from high-fat diet-induced insulin resistance and provide strong evidence that HSP induction in skeletal muscle could be a potential therapeutic treatment for obesity-induced insulin resistance.

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Deoxyglucose / metabolism
  • Dietary Fats / adverse effects*
  • Glucose Tolerance Test
  • HSP72 Heat-Shock Proteins / genetics*
  • Hot Temperature / therapeutic use*
  • I-kappa B Kinase / metabolism
  • Insulin Resistance / physiology*
  • Male
  • Mannitol / metabolism
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / physiology*
  • Rats
  • Rats, Wistar


  • Blood Glucose
  • Dietary Fats
  • HSP72 Heat-Shock Proteins
  • Mannitol
  • Deoxyglucose
  • I-kappa B Kinase