Heat Treatment Improves Glucose Tolerance and Prevents Skeletal Muscle Insulin Resistance in Rats Fed a High-Fat Diet

Abstract

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-MaleWistar rats were fed a high-fat diet (60% calories from fat) for 12 weeks and received a lower-body heat treatment (41°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 NH 2 -terminal kinase (JNK) and inhibitor of B kinase (IKK-␤), stress kinases implicated in insulin resistance, and upregulation of HSP72 and HSP25, proteins previously shown to inhibit JNK and IKK-␤ 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 obesityinduced insulin resistance. Diabetes 58:567-578, 2009

Heat stress induces mitochondrial adaptations in skeletal muscle

“…Incidentally, a previous study reported that a high-fat diet feeding also leads to mitochondrial biogenesis in skeletal muscle 21) . However, in another high-fat diet study, heat stress canceled mitochondrial biogenesis in rat skeletal muscle (hindlimbs hot bathing, 41ºC, 20 min) 5) , indicating that the additive effects of heat stress on mitochondrial adaptations are not universally observed. Thus, it could be notable that there are additive effects of heat stress on exercise training-induced mitochondrial biogenesis.…”

“…Therapeutic effects of heat stress on insulin resistance have been reported in type 2 diabetes of rodents (hindlimb hot bathing, 41ºC, 20 min) 5) and patients (Hot tub bathing, 37.8-41.0ºC, 30 min/ day, 6 days/week, 3 weeks) 6) , mediated by up-regulated glucose uptake in skeletal muscles, based on a mechanistic study investigating isolated skeletal muscle (42ºC, 30 min) 7) . In addition to glucose metabolism, several lines of evidence demonstrated various adaptabilities of mitochondria-centered oxidative metabolism by heat stress.…”

Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system

“…HSPs act as molecular chaperones, and the expression can increase in response to physical and chemical stressors as well as oxidative stress. Several laboratories (21,35) have demonstrated that induction of HSPs by heat treatment can protect against obesity-related insulin resistance and that an increased expression of HSP70 and HSP25 plays a significant role in protecting SM from the development of age-related insulin resistance (20). Moreover, the small HSPs especially protect against ROS and stress situations such as ATP depletion (1).…”

Targeting Molecular Chaperones in Diabetic Peripheral Neuropathy

“…Despite the lack of proper controls and its exploratory nature, the credibility of this early report has been substantiated by similar studies from animal models of DM. For example, whereas high-fat diet evoked significant hyperglycemia, hyperinsulinemia, insulin insensitivity, glucose intolerance as well as JNK and IKKactivation in skeletal muscles in rodents, weekly heat therapy upregulated HSP70 which paralleled an apparent attenuation of these metabolic characteristics (Chung et al, 2008;Gupte et al, 2009b). Chung et al further demonstrated that targeted overexpression of HSP70 in mouse skeletal muscles mimicked the effects of heat therapy in preventing fat-induced JNK phosphorylation, insulin resistance and fat deposition, suggesting that HSP70 might mediate the beneficial effects afforded by heat therapy (Chung et al, 2008).…”