The emerging role of the Hippo signaling pathway in interorgan crosstalk

Area of Science:

• Cell Biology
• Physiology
• Endocrinology

Background:

• Interorgan communication is vital for homeostasis; its disruption links to metabolic diseases, inflammation, and cancer.
• The Hippo signaling pathway, known for organ size control, now integrates systemic cues like hormones, metabolites, and microbes.
• This pathway acts as a bidirectional hub, interpreting systemic inputs and generating outputs that link organ systems.

Purpose of the Study:

• To review how Hippo signaling integrates diverse stimuli within key interorgan axes.
• To summarize the role of organ-specific Hippo activity in generating systemic metabolic outputs.
• To highlight the context-specific mechanisms enabling Hippo signaling adaptation.

Main Methods:

• Literature review of studies on Hippo signaling and interorgan communication.
• Analysis of Hippo pathway integration within gut-liver, gut-pancreas, and adipose-peripheral axes.
• Focus on Hippo signaling's role in adipose tissue and skeletal muscle metabolism.

Main Results:

• Hippo signaling integrates hormonal, metabolic, and microbial signals across organs.
• Adipose tissue and skeletal muscle Hippo activity generate systemic outputs impacting metabolism.
• Context-specific mechanisms allow Hippo signaling to adapt to physiological and pathological states.

Conclusions:

• Hippo signaling is a critical coordinator of interorgan communication and systemic homeostasis.
• Further research is needed to understand how Hippo signaling prioritizes and transmits signals across organs.
• Elucidating Hippo signaling mechanisms offers a unifying framework for understanding systemic physiology and disease.