RDH1 suppresses adiposity by promoting brown adipose adaptation to fasting and re-feeding.

RDH1 suppresses adiposity by promoting brown adipose adaptation to fasting and re-feeding. Cell Mol Life Sci. 2019 Feb 20;: Authors: Krois CR, Vuckovic MG, Huang P, Zaversnik C, Liu CS, Gibson CE, Wheeler MR, Obrochta KM, Min JH, Herber CB, Thompson AC, Shah ID, Gordon SP, Hellerstein MK, Napoli JL Abstract RDH1 is one of the several enzymes that catalyze the first of the two reactions to convert retinol into all-trans-retinoic acid (atRA). Here, we show that Rdh1-null mice fed a low-fat diet gain more weight as adiposity (17% males, 13% females) than wild-type mice by 20 weeks old, despite neither consuming more calories nor decreasing activity. Glucose intolerance and insulin resistance develop following increased adiposity. Despite the increase in white fat pads, epididymal white adipose does not express Rdh1, nor does muscle. Brown adipose tissue (BAT) and liver express Rdh1 at relatively high levels compared to other tissues. Rdh1 ablation lowered body temperatures during ambient conditions. Given the decreased body temperature, we focused on BAT. A lack of differences in BAT adipogenic gene expression between Rdh1-null mice and wild-type mice, including Pparg, Prdm16, Zfp516 and Zfp521, indicated that the phenotype was not driven by brown adipose hyperplasia. Rather, Rdh1 ablation eliminated the increase in BAT atRA that occurs after re-feeding. This disruption of atRA homeostasis increased fatty acid uptake, but attenuated li...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research