Mesenteric adipose tissue contributes to intestinal barrier integrity and protects against nonalcoholic fatty liver disease in mice

Abstract

Visceral adipose tissue (VAT) is related to nonalcoholic fatty liver disease (NAFLD). However, the role of mesenteric adipose tissue (MAT), part of the VAT, in NAFLD is unclear. In the present study, we monitored the liver and four depots of the VAT in high-fat diet (HFD)-feeding mice at multiple time points (4, 8, and 12 wk). The MAT had become inflamed by the eighth week of HFD feeding, earlier than other depots of VAT. Furthermore, MAT removal after 8 wk of HFD resulted in more severe steatosis and more foci of inflammation infiltration, as well as higher NAFLD activity scores. Consistent with these findings, the mRNA expression of proinflammatory cytokines and lipid anabolism genes was increased in the livers of inflamed MAT-removal mice. MAT removal also injured the intestinal barrier and promoted intestinal inflammation. The bacterial load translocated to the liver and circulating levels of lipopolysaccha-ride were also evaluated in inflamed MAT-removal mice. In a cocul-ture experiment involving adipocytes and intestinal epithelial cells, mRNA expression of zonula occludens-1 (ZO-1), and occludin in CT-26 cells was upregulated and permeability of monolayer Caco-2 cells was elevated under stimulation from adipocytes or inflamed adipocytes. Taken together, these results demonstrated that MAT removal damaged the intestinal barrier and aggravated NAFLD and that MAT inflammation may be a compensatory response to protect the liver by maintaining the intestinal barrier. NEW & NOTEWORTHY The mesenteric adipose tissue (MAT) lies between the gut and liver and plays a critical role in hepatic metabolic diseases. In the present study, we found that the MAT was prone to inflammation in high-fat diet-fed mice. Removal of the inflamed MAT resulted in more hepatic inflammation, lipid accumulation, and decreased glucose tolerance. Furthermore, we showed that the MAT contributed to intestinal barrier integrity, thus clarifying why MAT removal aggravated nonalcoholic fatty liver disease.