Abstract
Excessive lipid accumulation in hepatocytes is a defining feature of non-alcoholic fatty liver disease (NAFLD), a condition that is becoming increasingly prevalent worldwide. While long non-coding RNAs (LncRNAs) have been implicated in hepatic lipid metabolism, the precise regulatory mechanisms they employ remain poorly understood. In this study, we investigate the role of AK142643, a previously uncharacterized LncRNA, in hepatic lipid metabolism and the development of NAFLD. Our results demonstrate that AK142643 is upregulated in the livers of ob/ob and high fat diet (HFD)-fed mice, and that it promotes hepatic lipid accumulation both in vivo and in vitro. Furthermore, we reveal that AK142643 acts through the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) to enhance the expression of fatty acid translocase (FAT)/CD36, a key regulator of lipid metabolism. Specifically, AK142643 facilitates the binding of IGF2BP2 to CD36 mRNA, thereby increasing its stability and promoting its expression. Taken together, these findings shed new light on the complex interplay between LncRNAs and hepatic lipid metabolism, and provide insights into the mechanisms underlying the development of NAFLD.