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

Transcriptome sequencing revealed TA-activated fatty acid (FA) degradation and FA metabolism signaling pathways. Moreover, western blot-ting 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 accu-mulation 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.