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

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

Fathima N Cassim Bawa

Yanyong Xu

Raja Gopoju

Noel-Marie Plonski

Amy Shiyab

Shuwei Hu

Shaoru Chen

Yingdong Zhu

Kavita Jadhav

Takhar Kasumov

Yanqiao Zhang

2022

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 (RARα) in mediating the effect of AtRA on hepatosteatosis in mice. Hepatocyte-specific Rarα-/- (L-Rarα-/- ) 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 RARα-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-Rarα-/- mice. Furthermore, AtRA reduced hepatocyte fatty acid uptake and lipid droplet formation, dependent on hepatocyte RARα. Our data suggest that hepatocyte RARα plays an important role in preventing hepatosteatosis and mediates AtRA's effects on diet-induced hepatosteatosis.

Hepatol Commun
. 2022 Oct;6(10):2665-2675. doi: 10.1002/hep4.2049. Epub 2022 Jul 19.

English

https://doi.org/10.1002/hep4.2049