title: Retinaldehyde represses adipogenesis and diet-induced obesity.
abstract: The metabolism of vitamin A and the diverse effects of its metabolites are tightly controlled by distinct retinoid-generating enzymes, retinoid-binding proteins and retinoid-activated nuclear receptors. Retinoic acid regulates differentiation and metabolism by activating the retinoic acid receptor and retinoid X receptor (RXR), indirectly influencing RXR heterodimeric partners. Retinoic acid is formed solely from retinaldehyde (Rald), which in turn is derived from vitamin A. Rald currently has no defined biologic role outside the eye. Here we show that Rald is present in rodent fat, binds retinol-binding proteins (CRBP1, RBP4), inhibits adipogenesis and suppresses peroxisome proliferator-activated receptor-gamma and RXR responses. In vivo, mice lacking the Rald-catabolizing enzyme retinaldehyde dehydrogenase 1 (Raldh1) resisted diet-induced obesity and insulin resistance and showed increased energy dissipation. In ob/ob mice, administrating Rald or a Raldh inhibitor reduced fat and increased insulin sensitivity. These results identify Rald as a distinct transcriptional regulator of the metabolic responses to a high-fat diet.
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Ouliana
authors.initials: O
authors.lastname: Ziouzenkova
authors.forename: Gabriela
authors.initials: G
authors.lastname: Orasanu
authors.forename: Molly
authors.initials: M
authors.lastname: Sharlach
authors.forename: Taro E
authors.initials: TE
authors.lastname: Akiyama
authors.forename: Joel P
authors.initials: JP
authors.lastname: Berger
authors.forename: Jason
authors.initials: J
authors.lastname: Viereck
authors.forename: James A
authors.initials: JA
authors.lastname: Hamilton
authors.forename: Guangwen
authors.initials: G
authors.lastname: Tang
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Dolnikowski
authors.forename: Silke
authors.initials: S
authors.lastname: Vogel
authors.forename: Gregg
authors.initials: G
authors.lastname: Duester
authors.forename: Jorge
authors.initials: J
authors.lastname: Plutzky
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004032:Diet / Q000009:adverse effects*; D005260:Female; D006131:Growth Inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D041681:NIH 3T3 Cells; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D011817:Rabbits; D012172:Retinaldehyde / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D006131:Growth Inhibitors; D012172:Retinaldehyde