The Transplantation of ω3 PUFA-Altered Gut Microbiota of fat-1 Mice to Wild-Type Littermates Prevents Obesity and Associated Metabolic Disorders

Diabetes. 2018 Aug;67(8):1512-1523. doi: 10.2337/db17-1488. Epub 2018 May 23.

Abstract

Altering the gut microbiome may be beneficial to the host and recently arose as a promising strategy to manage obesity. Here, we investigated the relative contribution of ω3 polyunsaturated fatty acid (PUFA)-mediated alterations in the microbiota to metabolic parameter changes in mice. Four groups were compared: male fat-1 transgenic mice (with constitutive production of ω3 PUFAs) and male wild-type (WT) littermates fed an obesogenic (high fat/high sucrose [HFHS]) or a control diet. Unlike WT mice, HFHS-fed fat-1 mice were protected against obesity, glucose intolerance, and hepatic steatosis. Unlike WT mice, fat-1 mice maintained a normal barrier function, resulting in a significantly lower metabolic endotoxemia. The fat-1 mice displayed greater phylogenic diversity in the cecum, and fecal microbiota transplantation from fat-1 to WT mice was able to reverse weight gain and to normalize glucose tolerance and intestinal permeability. We concluded that the ω3 PUFA-mediated alteration of gut microbiota contributed to the prevention of metabolic syndrome in fat-1 mice. It occurred independently of changes in the PUFA content of host tissues and may represent a promising strategy to prevent metabolic disease and preserve a lean phenotype.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Diet, Carbohydrate Loading / adverse effects
  • Diet, High-Fat / adverse effects
  • Dietary Sucrose / adverse effects
  • Dysbiosis / microbiology
  • Dysbiosis / physiopathology
  • Dysbiosis / therapy
  • Endotoxemia / etiology
  • Endotoxemia / prevention & control
  • Fatty Acids, Omega-3 / metabolism*
  • Fecal Microbiota Transplantation* / adverse effects
  • Gastrointestinal Microbiome*
  • Glucose Intolerance / microbiology
  • Glucose Intolerance / pathology
  • Glucose Intolerance / physiopathology
  • Glucose Intolerance / prevention & control*
  • Insulin Resistance*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology
  • Intestines / microbiology
  • Intestines / pathology
  • Intestines / physiopathology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice, Transgenic
  • Muscle, Skeletal / metabolism
  • Non-alcoholic Fatty Liver Disease / microbiology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Obesity / microbiology
  • Obesity / pathology
  • Obesity / physiopathology
  • Obesity / prevention & control*
  • Permeability
  • Phylogeny

Substances

  • Cadherins
  • Dietary Sucrose
  • Fatty Acids, Omega-3
  • fat1 protein, mouse