Reduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice.
Nat Commun
; 15(1): 4393, 2024 May 23.
Article
in En
| MEDLINE
| ID: mdl-38782937
ABSTRACT
Whether intestinal Leucine-rich repeat containing G-protein-coupled receptor 4 (LGR4) impacts nutrition absorption and energy homeostasis remains unknown. Here, we report that deficiency of Lgr4 (Lgr4iKO) in intestinal epithelium decreased the proportion of enterocytes selective for long-chain fatty acid absorption, leading to reduction in lipid absorption and subsequent improvement in lipid and glucose metabolism. Single-cell RNA sequencing demonstrates the heterogeneity of absorptive enterocytes, with a decrease in enterocytes selective for long-chain fatty acid-absorption and an increase in enterocytes selective for carbohydrate absorption in Lgr4iKO mice. Activation of Notch signaling and concurrent inhibition of Wnt signaling are observed in the transgenes. Associated with these alterations is the substantial reduction in lipid absorption. Decrement in lipid absorption renders Lgr4iKO mice resistant to high fat diet-induced obesity relevant to wild type littermates. Our study thus suggests that targeting intestinal LGR4 is a potential strategy for the intervention of obesity and liver steatosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Enterocytes
/
Receptors, G-Protein-Coupled
/
Lipid Metabolism
/
Diet, High-Fat
/
Intestinal Mucosa
/
Obesity
Limits:
Animals
Language:
En
Journal:
Nat Commun
/
Nature communications
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Reino Unido