title: Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice.
abstract: 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.
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.|John S McIlhenny Skeletal Muscle Physiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Yan Y
authors.initials: YY
authors.lastname: Lam
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Connie W Y
authors.initials: CW
authors.lastname: Ha
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.|Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jenny M A
authors.initials: JM
authors.lastname: Hoffmann
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Oscarsson
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Anuwat
authors.initials: A
authors.lastname: Dinudom
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Mather
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Cook
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Hunt
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Caterson
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Holmes
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Len H
authors.initials: LH
authors.lastname: Storlien
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D010539:Permeability; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids