Technical Abstract: Vitamin A metabolism and the diverse effects of its metabolic products are tightly controlled, as evident by distinct retinoid generating enzymes, retinoid binding proteins, and nuclear receptors activated by cognate interactions with specific retinoids. The role of retinoic acid (RA) in differentiation and metabolism depends on transcription regulation of RA receptor and other heterodimeric partners of the retinoid X receptor (RXR). RA is formed solely from retinaldehyde (Rald) while Rald derives from multiple substrates, including vitamin A. Rald is considered primarily an RA precursor, with no defined biologic role outside the eye. Here we show Rald is present in rodent fat, binds to intracellular and circulating retinol binding proteins (CRBP1, RBP4), inhibits adipogenesis, and suppresses peroxisome proliferator-activated receptor'a(PPARa) and RXR responses. In vivo, mice lacking the Rald-catabolizing enzyme Raldh1 (Raldh-/-) resist high fat diet-induced obesity and insulin resistance while increasing energy expenditure. In ob/ob mice, Rald or citral (a Raldh inhibitor) administration markedly reduces fat and increases insulin sensitivity; all-trans RA and vitamin A did not have similar effects. These results identify Rald as a novel transcriptionally-active vitamin metabolite present in fat that limits obesity and insulin resistance induced by high-fat diet in mice.