Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth [article]

Andrew Cox, Allison Tsomides, Dean Yimlamai, Katie Hwang, Joel Miesfeld, Giorgio Galli, Brendan Fowl, Michael Fort, Kimberly Ma, Mark Sullivan, Aaron Hosios, Erin Snay (+11 others)
2018 bioRxiv   pre-print
The Hippo pathway and its nuclear effector Yap regulate organ size and cancer formation. While many modulators of Hippo activity have been identified, little is known about the Yap target genes that mediate these growth effects. Here, we show that yap-/- mutant zebrafish exhibit defects in hepatic progenitor potential and liver growth due to impaired glucose transport and nucleotide biosynthesis: transcriptomic and metabolomic analyses reveal that Yap regulates expression of glucose transporter
more » ... glucose transporter glut1, causing decreased glucose uptake and use for nucleotide biosynthesis in yap-/- mutants, and impaired glucose tolerance in adults. Nucleotide supplementation improved Yap-deficiency phenotypes, indicating functional importance of glucose-fuelled nucleotide biosynthesis. Yap-regulated Glut1 expression and glucose uptake are conserved in mammals, suggesting that stimulation of anabolic glucose metabolism is an evolutionarily conserved mechanism by which the Hippo pathway controls organ growth. Together, our results reveal a central role for Hippo signalling in metabolic homeostasis.
doi:10.1101/300053 fatcat:4yme2gzj4zgvrnudr232b66664