Replication of Obesity and Associated Signaling Pathways Through Transfer of Microbiota From Obese-Prone Rats

  1. Mihai Covasa1,2,4,5
  1. 1UMR1913-Microbiologie de l’Alimentation au Service de la Santé, l’Institut National de la Recherche Agronomique, Jouy-en-Josas, France
  2. 2UMR1913-Microbiologie de l’Alimentation au Service de la Santé, AgroParisTech, Jouy-en-Josas, France
  3. 3Doctoral School of Physiology and Pathophysiology, University Pierre and Marie Currie, Paris, France
  4. 4Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA
  5. 5Department of Human Health and Development, University of Suceava, Suceava, Romania
  1. Corresponding author: Mihai Covasa, mcovasa{at}jouy.inra.fr.
  1. F.A.D. and Y.S. contributed equally to this study.

Abstract

Aberrations in gut microbiota are associated with metabolic disorders, including obesity. However, whether shifts in the microbiota profile during obesity are a characteristic of the phenotype or a consequence of obesogenic feeding remains elusive. Therefore, we aimed to determine differences in the gut microbiota of obese-prone (OP) and obese-resistant (OR) rats and examined the contribution of this microbiota to the behavioral and metabolic characteristics during obesity. We found that OP rats display a gut microbiota distinct from OR rats fed the same high-fat diet, with a higher Firmicutes-to-Bacteroidetes ratio and significant genera differences. Transfer of OP but not OR microbiota to germ-free (GF) mice replicated the characteristics of the OP phenotype, including reduced intestinal and hypothalamic satiation signaling, hyperphagia, increased weight gain and adiposity, and enhanced lipogenesis and adipogenesis. Furthermore, increased gut permeability through conventionalization resulted in inflammation by proinflammatory nuclear factor (NF)-κB/inhibitor of NF-κB kinase subunit signaling in adipose tissue, liver, and hypothalamus. OP donor and GF recipient animals harbored specific species from Oscillibacter and Clostridium clusters XIVa and IV that were completely absent from OR animals. In conclusion, susceptibility to obesity is characterized by an unfavorable microbiome predisposing the host to peripheral and central inflammation and promoting weight gain and adiposity during obesogenic feeding.

Footnotes

  • Received October 3, 2013.
  • Accepted January 5, 2014.

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  1. Diabetes vol. 63 no. 5 1624-1636
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