The negative physiological impact of obesity is seen in alterations of the form and function of many organs, including growth of specific tissues and metabolic disturbances that contribute to the persistence of hyperphagia and weight gain and the incidence of associated diseases. We find that obesity causes lasting effects in intestinal epithelial stem cells, such that isolated stem cells from obese compared to lean mice proliferate at different rates and result in alterations in the cellular make-up and tissue function. We utilize in vivo and in vitro rodent models to identify how diet or factors related to obesity (ie. growth factors and autonomic neural plasticity) may induce these changes. These data suggest that the impact of obesity may not only affect differentiated cells of a tissue, but may be set earlier during cellular proliferation and drive the negative effects on tissue function.
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