High-fat diet impairs muscle function and increases the risk of environmental heatstroke in mice

Abstract Background. Environmental heat-stroke (HS) is a life-threatening response often triggered by a hot and humid weather. HS is characterized by an abnormal increase in body temperature (>40°C) causing dysfunction of organs, central nervous system, and that may end in death. Several lines of evidence indicate that environmental HS is caused by excessive heat production in skeletal muscle, which in turn is the result of abnormal Ca2+ leak from the sarcoplasmic reticulum (SR) and excessive production of oxidative species of oxygen and nitrogen (ROS and NOS). Methods. As high fat diet is known to increase oxidative stress, the objective of the present study was to investigate the effects of 3 months of high-fat diet (HFD) on HS susceptibility of wild type (WT) mice. HS susceptibility was tested in an environmental chamber where 4 months old mice (adult) were exposed to heat stress (41°C for 1 hr). Results. In comparison with mice fed with a regular diet, mice subjected to 3 months of HFD showed: a) increased body weight and accumulation of adipose tissue; b) elevated oxidative stress in both EDL and Soleus muscles (assessed by western blot of 3-NT levels and of expression of antioxidant enzymes such as SODs and Catalase) ; c) increased heat generation and oxygen consumption during exposure to environmental heat stress (oxygen consumption was assessed by indirect calorimetry) ; and finally d) enhanced sensitivity to both temperature and caffeine of isolated EDL and Soleus muscles during in vitro contracture test (IVCT), i.e. the gold standard procedure used to verify in-vitro HS susceptibility.Conclusions. The data collected suggest that HFD predisposes WT mice to HS, possibly as a result of elevated myoplasmic Ca2+ (indirectly assessed by IVCT) and increased oxidative stress (directly assessed by WB). These results could in principle have implications for the development of guidelines regarding food intake during periods of intense environmental heat.