Mitochondrial function in intestinal epithelium homeostasis and modulation in diet-induced obesity

Background: Systemic low-grade inflammation observed in diet-induced obesity has been associated with dysbiosis and disturbance of intestinal homeostasis. This latter relies on an efficient epithelial barrier and coordinated intestinal epithelial cell (IEC) renewal that are supported by their mitochondrial function. However, IEC mitochondrial function might be impaired by high fat diet (HFD) consumption, notably through gut-derived metabolite production and fatty acids, that may act as metabolic perturbators of IEC. Scope of review: This review presents the current general knowledge on mitochondria, before focusing on IEC mitochondrial function and its role in the control of intestinal homeostasis, and featuring the known effects of nutrients and metabolites, originating from the diet or gut bacterial metabolism, on IEC mitochondrial function. It then summarizes the impact of HFD on mitochondrial function in IEC of both small intestine and colon and discusses the possible link between mitochondrial dysfunction and altered intestinal homeostasis in diet-induced obesity. Major conclusions: HFD consumption provokes a metabolic shift toward fatty acid beta-oxidation in the small intestine epithelial cells and impairs colonocyte mitochondrial function, possibly through downstream consequences of excessive fatty acid beta-oxidation and/or the presence of deleterious metabolites produced by the gut microbiota. Decreased levels of ATP and concomitant O-2 leaks into the intestinal lumen could explain the alterations of intestinal epithelium dynamics, barrier disruption and dysbiosis that contribute to the loss of epithelial homeostasis in diet-induced obesity. However, the effect of HFD on IEC mitochondrial function in the small intestine remains unknown and the precise mechanisms by which HFD induces mitochondrial dysfunction in the colon have not been elucidated so far. (c) 2022 The Authors. Published by Elsevier GmbH.

Automated summary

This review discusses the impact of high-fat diet on mitochondrial function in intestinal epithelial cells and its role in regulating intestinal homeostasis. The findings suggest that high-fat diet may disrupt intestinal epithelial barrier, dysbiosis, and loss of epithelial homeostasis through its effects on mitochondrial function.