Insulin regulates retinol dehydrogenase expression and all-trans-retinoic acid biosynthesis through FoxO1

摘要: All-trans-retinoic acid (atRA), an autacoid derived from retinol (vitamin A), regulates energy balance and reduces adiposity. We show that status atRA biosynthesis at the rate-limiting step, catalyzed by dehydrogenases (RDH). Six h after re-feeding, Rdh1 expression decreased 80–90% in liver brown adipose tissue Rdh10 was 45–63% liver, pancreas, kidney, all relative to mice fasted 16 h. 44% 3 reduced Rdh expression. Oral gavage with glucose or injection insulin mRNA 50% greater mouse liver. Removing serum medium of human hepatoma cell line HepG2 increased Rdh16 (human ortholog) 2–3-fold 4 h, increasing transcription stabilizing mRNA. Insulin cells incubated serum-free inhibiting destabilizing action required PI3K Akt, which suppress FoxO1. Serum removal 4-fold cells, whereas dominant-negative FoxO1 prevented increase. Thus, via regulate biosynthesis. These results reveal mechanisms for regulating opposing effects on gluconeogenesis, also suggest interaction between signaling related diseases, such as type II diabetes cancer.