Nutritional status dictates the rate and mode of intestinal epithelial stem cell proliferation through an AMPK dependent mechanism
type: CreativeWork
description: Obesity is the leading cause of preventable chronic disease, such as diabetes, heart disease and cancer. The most significant factor driving obesity and the development of these secondary disorders is diet. There is significant evidence that the amount of food one eats induces adaptational growth and functional changes of several tissues, including bone, skin, adipose, liver and intestinal tissue. Understanding how the amount of food induces these changes may reveal mechanisms by which we can manipulate to reverse the negative impact of obesity on tissue size and function. One tissue significantly impacted by obesity is the intestinal epithelium. It is known that the amount of food, and not the type of diet, drives changes in tissue size by increasing the number of epithelial cells, villi height and crypt depth. Because increases in tissue size are under the control of stem cells located within the tissue, I investigated if and how the amount of food may drive increases in the rate and mode (asymmetric vs. symmetric) of stem proliferation. In vivo, 48 male C57/B6 mice were used. Mice were fed varying amounts of chow diet and were separated into 4 groups; 1) ab libitum (adlib) fed 2) fifty-percent (50%) of their average consumption 3) fasted or 4) fasted-refed. Mice were sacrificed and the small intestine was excised and immunohistochemically processed to determine the rate of stem cell proliferation and the mode of division. The results revealed that adlib fed animals showed a higher % of symmetrically dividing cells compared with the 50% and fasted animals. An increase in symmetric division results in an increase in the pool of stem cells and expansion of the tissue size. In order to investigate the mechanism driving nutrient-driven changes in the mode of stem cell division, in vitro analysis of intestinal epithelial organoids (primary isolated intestinal epithelial crypts allowed to grow into fully functional tissue) were used. In vivo analysis was mimicked by var…
abstract: Obesity is the leading cause of preventable chronic disease, such as diabetes, heart disease and cancer. The most significant factor driving obesity and the development of these secondary disorders is diet. There is significant evidence that the amount of food one eats induces adaptational growth and functional changes of several tissues, including bone, skin, adipose, liver and intestinal tissue. Understanding how the amount of food induces these changes may reveal mechanisms by which we can manipulate to reverse the negative impact of obesity on tissue size and function. One tissue significantly impacted by obesity is the intestinal epithelium. It is known that the amount of food, and not the type of diet, drives changes in tissue size by increasing the number of epithelial cells, villi height and crypt depth. Because increases in tissue size are under the control of stem cells located within the tissue, I investigated if and how the amount of food may drive increases in the rate and mode (asymmetric vs. symmetric) of stem proliferation. In vivo, 48 male C57/B6 mice were used. Mice were fed varying amounts of chow diet and were separated into 4 groups; 1) ab libitum (adlib) fed 2) fifty-percent (50%) of their average consumption 3) fasted or 4) fasted-refed. Mice were sacrificed and the small intestine was excised and immunohistochemically processed to determine the rate of stem cell proliferation and the mode of division. The results revealed that adlib fed animals showed a higher % of symmetrically dividing cells compared with the 50% and fasted animals. An increase in symmetric division results in an increase in the pool of stem cells and expansion of the tissue size. In order to investigate the mechanism driving nutrient-driven changes in the mode of stem cell division, in vitro analysis of intestinal epithelial organoids (primary isolated intestinal epithelial crypts allowed to grow into fully functional tissue) were used. In vivo analysis was mimicked by var…
author: Blackmore, Katherine Anne
language: en
keywords: Stem cell, Crypt, Food intake, Symmetric division, Liver Kinase B, AMP kinase pathway
date published: 2016-11-10T17:50:06Z
date modified: 2026-07-22T22:26:35Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/92752