Heat therapy attenuates hepatic lipid accumulation via CSAD-driven metabolic reprogramming of fatty acid oxidation.

OBJECTIVE

Non-alcoholic fatty liver disease (NAFLD) represents a significant global health challenge, predominantly managed through non-pharmacological interventions. Heat therapy (HT) has been shown to effectively reduce hepatic lipid accumulation; however, the underlying mechanisms remain incompletely understood. This study aims to elucidate the mechanism by liver metabolomics.

METHODS

This animal study utilized a high-fat diet to induce hepatic lipid accumulation in mice, combined with long-term HT intervention. Subsequently, metabolomic profiling and Western blot analysis were performed to assess hepatic metabolic alterations and elucidate the underlying mechanisms of HT action, followed by in vitro validation using L02 human hepatocytes.

RESULTS

HT significantly decreased body weight, fat levels, and hepatic lipid accumulation while preventing excessive glycogen depletion in HFD-fed mice. Metabolomics analysis revealed that HT reduced diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA), and saturated ceramides (CER); it also increased taurine levels, enhanced the utilization of vitamins B2, B5, and B6, and corrected amino acid imbalances. Furthermore, HT upregulated the expression of CSAD, ACADL, and ATP5A. In vitro studies demonstrated that heat treatment increased CSAD levels in L02 cells. Overexpression of CSAD elevated taurine levels and, under palmitic acid induction, reduced FFA levels while upregulating VDAC1 and ATP5A.

CONCLUSIONS

HT enhances mitochondrial function and promotes fatty acid oxidation by upregulating taurine synthesis via CSAD, thereby inhibiting hepatic lipid accumulation and correcting metabolic disorders, ultimately improving NAFLD.