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

• Published in: Molecular nutrition & food research Vol. 59; no. 5; pp. 968 - 978
• Main Authors: Kless, Caroline, Müller, Veronika Maria, Schüppel, Valentina Luise, Lichtenegger, Martina, Rychlik, Michael, Daniel, Hannelore, Klingenspor, Martin, Haller, Dirk
• Format: Journal Article
• Language: English
• Published: Germany Wiley-VCH 01.05.2015; Blackwell Publishing Ltd
• Subjects: adipose tissue; Adipose Tissue - metabolism; Animals; body fat; Colon - metabolism; comorbidity; Diet, High-Fat; Diet-induced obesity; dietary fat; digestive system; Endotoxemia - etiology; genetic background; Glucose - metabolism; Glucose tolerance; Gut barrier integrity; High-fat diet; Homeostasis; lard; Liver - immunology; Male; metabolic diseases; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Mouse strains; obesity; Obesity - metabolism; Species Specificity; Glucose tolerance; Gut barrier integrity; Mouse strains; Diet-induced obesity; High-fat diet
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.201400840

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.