Deleterious Impacts of Western diet on Jejunum Function and Health are Reversible

Background: The goal of this study was to determine whether the influence of high-fat high-sugar diet (Western diet) on intestinal function and health was reversible. Methods: We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from male C57Bl/6J mice randomly assigned to one of the following groups for the study duration: high-fat high-sugar diet for 24-weeks (HFHS), HFHS diet for 12-weeks then switched to standard chow and water for a further 12 weeks (Std), and lean controls (standard chow and water for 24-weeks). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum and tissue assays were performed. Results: Basal Isc was significantly decreased (by 42%, P<0.05) in HFHS versus leans. This decrease in I_sc was fully reversed by switching to Std diet. The HFHS-induced decrease in Isc was attributed to a significant loss of ClC2 expression. Changes in inflammatory state (TNF-Alpha) and intestinal health (MPO activity) were associated with body weight changes. Conclusions: Our data suggests that the reduced basal jejunal I_sc in HFHS mice is reversible. Better understanding of Western diet-mediated intestinal disturbances may permit for improved treatment options for gastrointestinal disturbances in obese individuals.