Program on Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Endocrinology. 2010 May;151(5):2078-86. doi: 10.1210/en.2009-0850. Epub 2010 Feb 26.
The exact mechanisms through which ghrelin promotes lipogenesis are unknown. Uncoupling protein (UCP)-2 is a mitochondrial protein important in regulating reactive oxygen species; however, recent research shows that it may play an important role fat metabolism. Given that ghrelin increases UCP2 mRNA in white adipose tissue, we examined whether the lipogenic actions of ghrelin are modulated by UCP2 using ucp2(+/+) and ucp2(-/-) mice. Chronic ghrelin treatment either via osmotic minipumps or daily ip injections induced body weight gain in both ucp2(+/+) and ucp2(-/-) mice; however, body weight gain was potentiated in ucp2(-/-) mice. Increased body weight gain was completely due to increased body fat as a result of decreased fat oxidation in ucp2(-/-) mice. Ghrelin treatment of ucp2(-/-) mice resulted in a gene expression profile favoring lipogenesis. In a calorie-restriction model of negative energy balance, ghrelin to ucp2(+/+) mice did not increase body weight; however, ghrelin to ucp2(-/-) mice still induced body weight. These results show that UCP2 plays an important role in fat metabolism by promoting fat oxidation and restricts ghrelin-induced lipogenesis.
瘦素促进脂肪生成的确切机制尚不清楚。解偶联蛋白（UCP）-2 是一种在线粒体中起重要作用的蛋白质，可调节活性氧；然而，最近的研究表明，它可能在脂肪代谢中发挥重要作用。鉴于瘦素增加白色脂肪组织中的 UCP2 mRNA，我们研究了 UCP2 是否调节瘦素的脂肪生成作用，使用了 ucp2(+/+) 和 ucp2(-/-) 小鼠。通过渗透型迷你泵或每日腹腔注射慢性给予瘦素治疗，可引起 ucp2(+/+) 和 ucp2(-/-) 小鼠体重增加；然而，ucp2(-/-) 小鼠的体重增加更为明显。体重增加完全是由于 ucp2(-/-) 小鼠的脂肪氧化减少导致体脂增加。瘦素处理 ucp2(-/-) 小鼠导致有利于脂肪生成的基因表达谱。在负能量平衡的热量限制模型中，ghrelin 治疗 ucp2(+/+) 小鼠不会增加体重；然而，ghrelin 治疗 ucp2(-/-) 小鼠仍会诱导体重增加。这些结果表明，UCP2 通过促进脂肪氧化在脂肪代谢中起重要作用，并限制瘦素诱导的脂肪生成。
