Rdh1 supresses adiposity by promoting brown adipose adaptation to fasting and re-feeding

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 low-fat diet gain more weight as adiposity than wild-type mice by 20 weeks old, despite neither consuming more calories nor decreasing activity. RNAseq revealed dysregulation of 424 BAT genes in null mice, with segregated predominantly into differences after fasting vs after re-feeding. Rdh1-generated atRA in BAT regulates multiple genes that promote BAT adaptation to whole-body energy status, such as fasting and re-feeding. Transcriptome analysis of brown adipose tissue from Rdh1KO and WT mice after 16h fasting and 16h fasting followed by 6h re-feeding.Rdh1是催化视黄醇转化为全反式维甲酸（all-trans-retinoic acid, atRA）的两步酶促反应中，负责第一步反应的多种酶之一。本研究发现，低脂饲料喂养的Rdh1敲除（Rdh1-null）小鼠在20周龄时的脂肪蓄积程度显著高于野生型小鼠，尽管其摄热量并未增加，活动量也未出现下降。RNA测序（RNA-seq）结果显示，敲除小鼠的棕色脂肪组织（brown adipose tissue, BAT）中共存在424个基因表达失调，且这些基因的表达差异主要集中于禁食与复食两种实验条件下。Rdh1催化生成的atRA在棕色脂肪组织中，可调控一系列参与机体整体能量状态适应的基因，包括与禁食、复食过程相关的基因。本研究对Rdh1敲除（Rdh1KO）与野生型（WT）小鼠的棕色脂肪组织开展了转录组分析，相关小鼠分别接受16小时禁食处理，以及16小时禁食后再复食6小时的处理。