Retinaldehyde represses adipogenesis and diet-induced obesity.
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.
Ziouzenkova
Ouliana
O
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Orasanu
Gabriela
G
Sharlach
Molly
M
Akiyama
Taro E
TE
Berger
Joel P
JP
Viereck
Jason
J
Hamilton
James A
JA
Tang
Guangwen
G
Dolnikowski
Gregory G
GG
Vogel
Silke
S
Duester
Gregg
G
Plutzky
Jorge
J
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*
D006131:Growth Inhibitors; D012172:Retinaldehyde