Ectopic fat deposition in intestinal wall caused the increase of L cell pyroptosis mainly through local hypoxia.

PURPOSE: L-cell dysfunction occurs in people with obesity, characterized by alterations in glucagon-like peptide-1 (GLP-1) secretion.The mechanism of L-cell dysfunction in obesity is not clear. This study was to reveal the mechanisms of GLP-1 secretion change of intestinal L cells in an obesity state.

METHODS

The metabolic variables such as the body weight, fasting blood glucose, and blood lipids, GLP-1 secretion, local fat infiltration, hypoxia of the ileum in male mice fed with a high-fat diet (HFD, 60 % kcal from fat) and caloric-restriction diet (CRD, calories were 50 % of HFD group) were investigated. On this basis, intestinal L-cell line GLUTag cells were incubated in vitro under the environment of hypoxia or inflammation to investigate their function changes.

RESULTS

The body weight, fasting blood glucose, blood lipids and pro-inffammatories levels of the HFD mice were increased after 2 weeks of feeding. At 6 weeks, the existence of local hypoxia was detected. It appeared simultaneously with the decrease of GLP-1 secretion and L-cell number in ileum. In GLUTag cells cultured under hypoxia conditions, expressions of pyrogenic products gasdermin D and IL-18 were increased, cell proliferation activity was inhibited, the overall number was decreased.

CONCLUSION

Ectopic fat deposition of the intestinal wall caused by obesity mainly leads to an exacerbatiion of L cell pyroptosis through local hypoxia.