Changes in colon luminal environment induced mitochondrial dysfunction of epithelial cells in obese mice

Background and objectives: Obesity and overweight are characterized by a systemic low-grade inflammation that has been associated with disturbances of intestinal homeostasis and dysbiosis. Energy metabolism, in particular through mitochondria, plays a central role in intestinal epithelial homeostasis. In addition, dietary modulations of the luminal environment may impact mitochondrial function. The aim of this study was to evaluate whether consumption of an obesogenic diet, also called western diet (WD), alters mitochondrial function of colonic epithelial cells (CEC) in mice. Methods: Male C57Bl/6J were fed a control diet (CTRL, 10% kcal from fat) or a WD (58% kcal from fat and drink water supplemented with fructose and sucrose at 42 g/L). After 22 weeks, CEC were isolated to assess mitochondrial function by Seahorse® technology while colonic content was collected to characterize microbiota, through 16S DNA analysis, and intestinal metabolites, via nuclear magnetic resonance and a methylene blue-based assay for sulfides. Results: WD mice developed obesity associated with hepatic steatosis and systemic endotoxemia (LPS-BP: 535.8±38.5 vs 668.7±39.7 ng/mL, P