image: Schematic illustration of high temperature ameliorated high-fat diet-induced insulin resistance in SMT of DIO mice. HT, high temperature (40℃, 4 h); DIO, diet-induced obesity; HSF1, heat shock factor 1; HSP70, heat shock protein 70; LD, lipid droplets; ASAH1, acid ceramidase N-acylsphingosine amidohydrolase 1.
Credit: Qiankun Wang, Lupeng Chen, Junzhi Zhang, Yue Liu, Yi Jin, Jian Wu, Zhuqing Ren
In contemporary society, obesity has emerged as a worldwide chronic metabolic disorder, imposing substantial burdens on both individual health and healthcare systems. The insulin resistance that accompanies obesity poses a serious threat to human health.
A recent study published in Life Metabolism reports that high temperature can ameliorate insulin resistance by promoting ceramide catabolism in skeletal muscle tissue (SMT) of obese mice.
The researchers utilized a diet-induced obese (DIO) mouse model and subjected them to either room temperature (RT) or high temperature (40°C) treatment (HT). They found that HT promoted SMT glycogen synthesis, increased the phosphorylation level of protein kinase B (AKT), and lowered blood glucose levels in SMT, indicating that HT improved insulin resistance (IR) in DIO mice. Additionally, HT can sustain the decay phase of heat shock factor 1 (HSF1), thereby activating the gene expression of heat shock proteins (HSPs). Metabolomic and lipidomic analyses of SMT indicated that HT promotes ceramide breakdown, leading to an increase in sphingomyelin and sphingosine. Further investigation revealed that the degradation of ceramides is dependent on the expression of the acid ceramidase N-acylsphingosine amidohydrolase 1 (ASAH1), and inhibition of ASAH1 can alleviate the high temperature-mediated insulin resistance of SMT in DIO mice.
This study revealed a previously unknown connection between high temperature exposure and sphingolipid metabolism in obesity, suggesting that HT can ameliorate IR by promoting sphingolipid degradation in SMT of obese mice. This groundbreaking discovery not only provides new insights into addressing obesity and insulin resistance but also offers theoretical support for the development of hyperthermia therapy as a novel strategy for treating obesity and metabolic diseases.
Journal
Life Metabolism