| RRC ID |
84051
|
| 著者 |
Liu CC, Khan A, Seban N, Littlejohn N, Shah A, Srinivasan S.
|
| タイトル |
A homeostatic gut-to-brain insulin antagonist restrains neuronally stimulated fat loss.
|
| ジャーナル |
Nat Commun
|
| 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 receptor and functions via FOXO and AMPK signaling in ASI neurons. Phylogenetic analysis suggests that INS-7 bears greater resemblance to members of the broad insulin/relaxin superfamily than to conventional mammalian insulin and IGF peptides. The discovery of an endogenous insulin antagonist secreted by specialized intestinal cells with enteroendocrine functions suggests unexpected and important properties of the intestine and its role in directing neuronal functions.
|
| 巻・号 |
15(1)
|
| ページ |
6869
|
| 公開日 |
2024-8-11
|
| DOI |
10.1038/s41467-024-51077-3
|
| PII |
10.1038/s41467-024-51077-3
|
| PMID |
39127676
|
| PMC |
PMC11316803
|
| MeSH |
Animals
Brain / drug effects
Brain / metabolism
Caenorhabditis elegans* / metabolism
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Fasting
Forkhead Transcription Factors / genetics
Forkhead Transcription Factors / metabolism
Homeostasis*
Insulin* / metabolism
Intestinal Mucosa / metabolism
Intestines
Neurons* / drug effects
Neurons* / metabolism
Neuropeptides / metabolism
Phylogeny
Receptor, Insulin / antagonists & inhibitors
Receptor, Insulin / metabolism
Signal Transduction / drug effects
|
| リソース情報 |
| 線虫 |
tm1907 |
