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

Andrew G Cox1, Allison Tsomides2, Dean Yimlamai3

  • 1Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA andrew.cox@petermac.org wolfram_goessling@hms.harvard.edu.

The EMBO Journal
|October 24, 2018
PubMed

Insights

The Hippo pathway, regulated by Yap, controls organ growth by influencing glucose metabolism. Yap deficiency impairs glucose uptake and nucleotide synthesis, highlighting its role in metabolic homeostasis.

Area of Science:

  • Cell Biology
  • Metabolic Regulation
  • Developmental Biology

Background:

  • The Hippo pathway and its effector Yap are key regulators of organ size and cancer.
  • While Hippo pathway modulators are known, Yap target genes mediating growth effects remain unclear.

Purpose of the Study:

  • To investigate Yap target genes involved in organ growth regulation.
  • To elucidate the role of the Hippo pathway in glucose metabolism and nucleotide biosynthesis.

Main Methods:

  • Zebrafish (Danio rerio) genetic models (yap-/- mutants).
  • Transcriptomic and metabolomic analyses.
  • Glucose tolerance tests and nucleotide supplementation experiments.

Main Results:

  • Yap deficiency in zebrafish impairs hepatic progenitor potential and liver growth.
  • Yap regulates glucose transporter glut1 expression, reducing glucose uptake and nucleotide biosynthesis.
  • Nucleotide supplementation rescues Yap deficiency phenotypes, confirming the importance of glucose-fueled nucleotide synthesis.
  • Yap-regulated glut1 expression and glucose uptake are conserved in mammals.

Conclusions:

  • The Hippo pathway, via Yap, plays a crucial role in glucose metabolic homeostasis.
  • Yap controls organ growth by stimulating anabolic glucose metabolism, a conserved mechanism.
  • This study reveals a novel link between Hippo signaling and glucose metabolism.
Keywords:
Hippo pathwayYapglucose metabolismglut1liver development

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