Traumatic acid inhibits ACSL4 associated lipid accumulation in adipocytes to attenuate high‐fat diet‐induced obesity

Abstract

AbstractObesity is a major health concern that lacks effective intervention strategies. Traumatic acid (TA) is a potent wound‐healing agent in plants, considered an antioxidant food ingredient. This study demonstrated that TA treatment significantly reduced lipid accumulation in human adipocytes and prevented high‐fat diet induced obesity in zebrafish. Transcriptome sequencing revealed TA‐activated fatty acid (FA) degradation and FA metabolism signaling pathways. Moreover, western blotting and quantitative polymerase chain reaction showed that TA inhibited the expression of long‐chain acyl‐CoA synthetase‐4 (ACSL4). Overexpression of ACSL4 resulted in the reversal of TA beneficiary effects, indicating that the attenuated lipid accumulation of TA was regulated by ACSL4 expression. Limited proteolysis‐mass spectrometry and microscale thermophoresis were then used to confirm hexokinase 2 (HK2) as a direct molecular target of TA. Thus, we demonstrated the molecular basis of TA in regulating lipid accumulation and gave the first evidence that TA may function through the HK2‐ACSL4 axis.