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

Abstract

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.

Identification of candidate genes associated with skin yellowness in yellow chickens

“…We showed that g.4478C>G in the upstream region of CD36 is significantly associated with chicken skin yellowness. Further transcription factor prediction showed that CC genotype in this SNP position has more RAR transcription factor binding sites than the GG genotype, and RAR has been reported to regulate CD36 expression ( Zhao et al, 2022 ) and affect fatty acid uptake ( Cassim Bawa et al, 2022 ). The results of dual fluorescein reporter assays in this study further suggested that the CC genotype has higher transcriptional activity than the GG genotype.…”

Adipocyte retinoic acid receptor α prevents obesity and steatohepatitis by regulating energy expenditure and lipogenesis

“…The influx of FFAs from adipose tissue, together with systemic low‐grade inflammation and increased hepatic DNL likely due to delayed glucose clearance, may cause lipotoxicity, ROS production, and apoptosis in the liver of Rarα Adi−/− mice, leading to the development and progression of NAFLD. We have previously shown that loss of RARα in hepatocytes induces hepatosteatosis via inhibiting lipid droplet formation and inducing fatty acid uptake [29]. Thus, adipocyte RARα and hepatocyte RARα regulate the development of hepatosteatosis via distinct mechanisms.…”

Hepatic FOXA3 overexpression prevents Western diet–induced obesity and MASH through TGR5

“…To determine intestinal fat absorption, mice were fasted for 6 h and then i.v. injected with tyloxapol (500 μg/kg) prior to gavage with olive oil (15 μl/g body weight) as described ( 19 , 22 ). Plasma TG levels were determined at indicated time points.…”