Impact of a high-fat diet on intestinal stem cells and epithelial barrier function in middle-aged female mice

A high-fat diet (HFD) or obesity-promoting diet is closely associated with metabolic diseases and intestinal tumors, particularly in middle-aged individuals (typically 45–64 years old). The intestinal epithelium constitutes a barrier that separates the host from the food and microbiota in the gut, and thus, a dysfunctional epithelium is associated with a number of diseases. However, the changes caused to the function of intestinal epithelium in response to an HFD have not been well-studied to date. In the present study, middle-aged female mice (12 months old) fed an HFD for a period of 14 weeks were used to determine the effects of HFD on the intestine. Characteristics including the body weight, fat deposition, glucose metabolism, inflammatory state and intestinal morphology were assessed, while the intestinal stem cell (ISC) counts and the ability of isolated intestinal crypts to form organoid bodies in 3D culture were examined. Intestinal epithelial barrier function, including secretory defense, tight junctions and cell apoptosis, were also studied. Morphologically, the HFD resulted in a mild reduction in the length of villi of the small intestine, the colon length and the depth of colon crypts. In addition, the ISC counts were increased in the small intestine and colon in HFD-fed mice. The ability of crypts to grow into organoids (mini-guts) was also increased in crypts obtained from mice fed an HFD, while HFD compromised the epithelial barrier function of the colon. These results demonstrated how an HFD affects the intestinal epithelium and highlighted the need to carefully consider dietary patterns.