The intestinal epithelium plays an essential role in nutrient absorption, satiety hormone release and immune barrier function. Maintenance of the epithelium is driven by continuous cell renewal by intestinal epithelial stem cells (IESCs) located in the intestinal crypts. Obesity affects this process and results in changes in the size and cellular make‐up of the tissue. In addition, isolated IESCs from obese mice have a reduced growth potential to develop into organoids in culture compared with IESCs from lean mice, indicating that obesity may produce long‐lasting effects on IESC proliferation and differentiation. Because the amount and type of diet contribute to obesity, we wanted to determine whether the amount (in kilocalories) or type of diet differentially alters IESC proliferation. C57BL/6J mice were fed two different diet combinations, a high‐fat diet or a Westernized high‐fat/high‐sugar diet. The high‐fat and control groups were as follows: 1) 60% high‐fat fed, 2) 10% low‐fat fed, and 3) 60% high‐fat pair fed (fed a high‐fat diet, but in equal kcal as that eaten by the low‐fat fed animals to keep them lean). The Westernized high‐fat/high‐sugar and control groups were as follows: 1) 31.8% high‐fat, 25% sugar fed, 2) 10.6% low‐fat, 25% sugar fed, and 3) 31.8% high‐fat, 25% sugar pair fed group (fed a high‐fat high‐sugar diet, but in equal kcal as that eaten by the low‐fat high‐sugar fed animals to keep them lean). After 3 months, IESCs were isolated from each mouse using antibody‐based fluorescent cell sorting and grown in media containing inhibitors of differentiation. Crypt development was tracked for 14 days post‐plating and glucose‐induced crypt cell proliferation was measured on day 14. We found that crypts developed from IESCs isolated from high‐fat fed, obese mice formed a reduced number and size of budding structures compared with low‐fat fed, lean mice and high‐fat pair fed, lean mice, while the number of crypts developed per area measured were the same between the groups. Furthermore, glucose increased the proliferation of crypts developed from IESCs isolated from both low‐fat fed, lean mice and high‐fat pair fed, lean mice, but had no effect on the proliferation of crypts developed from IESCs isolated from high‐fat fed, obese mice. In contrast, the mice in the Westernized diet groups ate equal kcal amounts of each diet, were equal in body weight, and there were no significant differences in crypt cell proliferation between the groups. These results suggest that factors related to obesity and not the type of diet (high‐fat or high‐fat/high‐sugar) are driving lasting effects on IESC proliferation.Support or Funding InformationUSDA Hatch ILLU‐538‐926
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Open Access
May 1, 2018
Derek A.G Barisas + 1
