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We previously reported hepatic ERK activation during obesity development to stimulate a neuronal relay system, consisting of afferent splanchnic nerves from the liver and efferent vagal nerves to the pancreas, thereby triggering adaptive \u03b2 cell proliferation. However, the mechanism linking obesity with the interorgan system originating in hepatic ERK activation remains unclear. Herein, we clarified that colonic inflammation promotes \u03b2 cell proliferation through this interorgan system from the liver to the pancreas. First, dextran sodium sulfate (DSS) treatment induced colonic inflammation and hepatic ERK activation as well as \u03b2 cell proliferation, all of which were suppressed by blockades of the neuronal relay system by several approaches. In addition, treatment with anti\u2013lymphocyte Peyer\u2019s patch adhesion molecule-1 (anti-LPAM1) antibody suppressed \u03b2 cell proliferation induced by DSS treatment. Importantly, high-fat diet (HFD) feeding also elicited colonic inflammation, and its inhibition by anti-LPAM1 antibody administration suppressed hepatic ERK activation and \u03b2 cell proliferation induced by HFD. Thus, colonic inflammation triggers adaptive \u03b2 cell proliferation via the interorgan mechanism originating in hepatic ERK activation. 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