State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
PLoS One. 2013 Apr 18;8(4):e61740. doi: 10.1371/journal.pone.0061740. Print 2013.
Evolutionarily conserved Hippo (Hpo) pathway plays a pivotal role in the control of organ size. Although the Hpo pathway regulates proliferation of a variety of epidermal cells, its function in non-ectoderm-derived cells is largely unknown.
METHODOLOGY/PRINCIPAL FINDINGS: Through methods including fat quantification assays, starvation assays, in vivo labeling assays, we show that overexpression of Hpo in Drosophila melanogaster fat body restricts Drosophila body growth and reduces fat storage through regulation of adipocyte proliferation rather than through influencing the size of fat cells and lipid metabolism, whereas compromising Hpo activity results in weight gain and greater fat storage. Furthermore, we provide evidence that Yorkie (Yki, a transcriptional coactivator that functions in the Hpo pathway) antagonizes Hpo to modulate fat storage in Drosophila.
CONCLUSIONS/SIGNIFICANCE: Our findings specify a role of Hpo in controlling mesoderm-derived cell proliferation. The observed anti-obesity effects of Hpo may indicate great potential for its utilization in anti-obesity therapeutics.
进化上保守的 Hippo（Hpo）途径在控制器官大小方面起着关键作用。尽管 Hpo 途径调节多种表皮细胞的增殖，但它在非表皮细胞中的功能在很大程度上是未知的。
方法/主要发现：通过包括脂肪定量测定、饥饿测定、体内标记测定在内的方法，我们表明在果蝇脂肪体中过表达 Hpo 会通过调节脂肪细胞增殖而不是通过影响脂肪细胞大小和脂质代谢来限制果蝇的身体生长和减少脂肪储存，而削弱 Hpo 活性则会导致体重增加和更多的脂肪储存。此外，我们提供了证据表明 Yorkie（Yki，Hpo 途径中的转录共激活因子）拮抗 Hpo 以调节果蝇中的脂肪储存。
结论/意义：我们的发现指定了 Hpo 在控制中胚层衍生细胞增殖中的作用。Hpo 观察到的抗肥胖作用可能表明其在抗肥胖治疗中的应用具有巨大潜力。
