Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice

• Published in: Obesity (Silver Spring, Md.) Vol. 23; no. 7; pp. 1429 - 1439
• Main Authors: Lam, Yan Y., Ha, Connie W.Y., Hoffmann, Jenny M.A., Oscarsson, Jan, Dinudom, Anuwat, Mather, Thomas J., Cook, David I., Hunt, Nicholas H., Caterson, Ian D., Holmes, Andrew J., Storlien, Len H.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-07-2015
• Subjects: Animals; BACTERIA; BUTYRATE; COLITIS; Diet, High-Fat - adverse effects; Dietary Fats - metabolism; Endocrinology & Metabolism; Endocrinology and Diabetes; Endokrinologi och diabetes; Fatty acids; Fatty Acids - metabolism; Gastrointestinal Microbiome - drug effects; INDUCED OBESITY; Inflammation - metabolism; INFLAMMATORY BOWEL DISEASES; INSULIN-RESISTANCE; INTESTINAL PERMEABILITY; Intestines - microbiology; MECHANISMS; Metabolic disorders; Mice; Mice, Inbred C57BL; Nutrition & Dietetics; Obesity - metabolism; Oils & fats; PATHOGENESIS; Permeability; RATS; Weight Gain - drug effects; Australia
• DOI: 10.1002/oby.21122
• EISSN: 1930-739X
• ISSN: 1930-7381

Objective
To distinguish the effects of dietary fat profile on gut parameters and their relationships with metabolic changes and to determine the capacity of n‐3 fatty acids to modify gut variables in the context of diet‐induced metabolic dysfunctions.
Methods
Mice received control or high‐fat diets emphasizing saturated (HFD‐sat), n‐6 (HFD‐n6), or n‐3 (HFD‐n3) fatty acids for 8 weeks. In another cohort, mice that were maintained on HFD‐sat received n‐3‐rich fish oil or resolvin D1 supplementation.
Results
HFD‐sat and HFD‐n6 induced similar weight gain, but only HFD‐sat increased index of insulin resistance (HOMA‐IR), colonic permeability, and mesenteric fat inflammation. Hydrogen sulfide‐producing bacteria were one of the major groups driving the diet‐specific changes in gut microbiome, with the overall microbial profile being associated with changes in body weight, HOMA‐IR, and gut permeability. In mice maintained on HFD‐sat, fish oil and resolvin D1 restored barrier function and reduced inflammation in the colon but were unable to normalize HOMA‐IR.
Conclusions
Different dietary fat profiles led to distinct intestinal and metabolic outcomes that are independent of obesity. Interventions targeting inflammation successfully restored gut health but did not reverse systemic aspects of diet‐induced metabolic dysfunction, implicating separation between gut dysfunctions and disease‐initiating and/or ‐maintaining processes.