Diet-induced obesity causes metabolic impairment independent of alterations in gut barrier integrity.

Scope: The causal relationship between diet-induced obesity and metabolic disorders is not clear yet. One hypothesis is whether the obese state or high-fat diet per se affects intestinal barrier function provoking metabolic comorbidities. Methods and results: In three independent experiments with AKR/J, SWR/J, or BL/6J mice, we addressed the impact of genetic background, excess body fat storage, duration of high-fat feeding, and quality/quantity of dietary fat on glucose tolerance and gut barrier integrity in vivo and ex vivo. Impaired glucose tolerance in diet-induced obese BL/6J and AKR/J mice was not accompanied by an altered intestinal barrier function. Enforced dietary challenge by prolonged feeding and increasing fat quantity in BL/6J mice still failed to aggravate metabolic and intestinal deterioration. Despite a low-grade inflammatory status in adipose tissue, barrier function of BL/6J mice fed lard high-fat diet revealed no evidence for a diet-induced loss in barrier integrity. Conclusion: None of our results provided any evidence that gut barrier function is a subject to dietary regulation and obesity per se seems not to cause gut barrier impairment.