Colonic inflammation triggers β cell proliferation during obesity development via a liver-to-pancreas interorgan mechanism.

Summary

In mouse models, colonic inflammation induced by DSS or high-fat diet activates hepatic ERK and a splanchnic–vagal neuronal relay to drive adaptive pancreatic β-cell proliferation. Blocking the neuronal pathway or inhibiting gut homing via anti-LPAM1 suppressed β-cell proliferation and hepatic ERK activation. The study identifies a gut-origin signal that tunes β-cell mass during obesity.

Key Findings

• DSS-induced colonic inflammation increased hepatic ERK activation and pancreatic β-cell proliferation; both were suppressed by blocking the neuronal relay.
• Anti-LPAM1 antibody reduced DSS-induced β-cell proliferation, implicating gut homing in the signaling pathway.
• High-fat diet elicited colonic inflammation; anti-LPAM1 suppressed hepatic ERK activation and β-cell proliferation under HFD.

Clinical Implications

Targeting colonic inflammation or the hepatic ERK–autonomic relay could become strategies to modulate β-cell adaptation in insulin resistance, potentially delaying hyperglycemia onset.

Limitations

• Findings are in animal models; human validation is lacking
• Specific sensory and effector neural components beyond splanchnic/vagal pathways were not fully dissected

Future Directions

Validate the gut–liver–pancreas axis in humans (biomarkers, imaging, neuromodulation), and test whether modulating colonic inflammation alters β-cell mass/function in metabolic disease.