A homeostatic gut-to-brain insulin antagonist restrains neuronally stimulated fat loss.

ABSTRACT: In C. elegans mechanisms by which peripheral organs relay internal state information to the nervous system remain unknown, although strong evidence suggests that such signals do exist. Here we report the discovery of a peptide of the ancestral insulin superfamily called INS-7 that functions as an enteroendocrine peptide and is secreted from specialized cells of the intestine. INS-7 secretion is stimulated by food withdrawal, increases during fasting and acts as a bona fide gut-to-brain peptide that attenuates the release of a neuropeptide that drives fat loss in the periphery. Thus, INS-7 functions as a homeostatic signal from the intestine that gates the neuronal drive to stimulate fat loss during food shortage. Mechanistically, INS-7 functions as an antagonist at the canonical DAF-2 rece

SUBMITTER: Liu CC 

PROVIDER: S-EPMC11316803 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature