Hepatic retinoic acid receptor alpha mediates all-trans retinoic acid's effect on diet-induced hepatosteatosis

All-trans retinoic acid (AtRA) is an active metabolite of vitamin A that influences many biological processes in development, differentiation, and metabolism. AtRA functions through activation of retinoid acid receptors (RARs). AtRA is shown to ameliorate hepatic steatosis, but the underlying mechanism is not well understood. In this study, we investigated the role of hepatocyte RAR alpha (RAR alpha) in mediating the effect of AtRA on hepatosteatosis in mice. Hepatocyte-specific Rar alpha(-/-) (L-Rar alpha(-/-)) mice and their control mice were fed a chow diet, high-fat diet (HFD), or a high-fat/cholesterol/fructose (HFCF) diet. Some of the mice were also treated with AtRA. Loss of hepatocyte RAR alpha-induced hepatosteatosis in chow-fed aged mice and HFD-fed mice. AtRA prevented and reversed HFCF diet-induced obesity and hepatosteatosis in the control mice but not in L-Rar alpha(-/-) mice. Furthermore, AtRA reduced hepatocyte fatty acid uptake and lipid droplet formation, dependent on hepatocyte RAR alpha. Our data suggest that hepatocyte RAR alpha plays an important role in preventing hepatosteatosis and mediates AtRA's effects on diet-induced hepatosteatosis.

Automated summary

The study revealed that hepatocyte RAR alpha plays a crucial role in preventing hepatosteatosis and mediating the effects of all-trans retinoic acid (AtRA) on diet-induced hepatosteatosis.