Drosophila Ste-20 Family Protein Kinase, Hippo, Modulates Fat Cell Proliferation

BACKGROUND: 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.