Involvement of orexin in lipid accumulation in the liver

Abstract Objectives Orexin, a hypothalamic neuropeptide, is involved in energy homeostasis and regulates motivated behaviors, including feeding and the awake-sleep cycle. Orexin-knockout (OX-KO) mice exhibit greater weight gain than wild-type (WT) mice, despite similar food intake, suggesting that OX-KO mice may have an altered metabolism for weight gain. However, the actual effects of orexin on the metabolism of mice remain unclear. Methods We compared the lipid metabolism of OX-KO and WT mice, with a focus on lipid metabolism in the liver. Results The livers of OX-KO mice were significantly larger than those of WT mice and were yellowish in appearance. Oil red O staining revealed that lipid accumulation in the livers of OX-KO mice was higher than that in WT mice. Hepatic triglyceride content in OX-KO mice was higher than that in WT mice. The total cholesterol level in the peripheral blood was higher in OX-KO mice than in WT mice, although no significant differences in free fatty acid and serum triglyceride levels were observed. In comparison with WT mice, OX-KO mice showed higher transcript levels of hepatic lipogenic genes encoding sterol regulatory element binding protein 1 and Cd36 and lower transcript levels of genes encoding fatty acid transporter protein 2/5, peroxisomal proliferator-activated receptor α, STAT-induced suppressor of cytokine signaling 3, and hormone-sensitive lipase. Moreover, tumor necrosis factor (TNF) α mRNA levels in the liver were significantly higher in OX-KO mice than in WT mice. Conclusions Orexin likely contributes to the regulation of lipid metabolism in the liver.