Replication of obesity and associated signaling pathways through transfer of microbiota from obese prone rat
- Frank A Duca1,2,3,*,
- Yassine Sakar1,2,*,
- Patricia Lepage1,2,
- Fabienne Devime1,2,
- Bénédicte Langelier1,2,
- Joël Doré1,2 and
- Mihai Covasa1,2,4,5⇑
- 1 UMR1913-MICALIS, INRA, Jouy-en-Josas, 78352, France
- 2 UMR1913-MICALIS, AgroParisTech, Jouy-en-Josas, 78352, France
- 3Doctoral School of Physiology and Pathophysiology, University Pierre and Marie Currie, Paris, 75005, France
- 4Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA, 91766, USA
- 5Department of Human Health and Development, University of Suceava, Suceava, 720229, Romania
- Corresponding Author: Mihai Covasa Email:
Aberrations in gut microbiota are associated with metabolic disorders, including obesity. However, whether shifts in microbiota profile during obesity is 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 distinct gut microbiota from obese-resistant OR rats fed the same high-fat diet, with a higher Firmicutes/Bacteroidetes ratio and significant genera differences. Transfer of OP but not OR microbiota to GF mice replicated the characteristics of the OP phenotype: 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 via proinflammatory NF-κB/IKKβ 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, promoting weight gain and adiposity during obesogenic feeding.
* FAD and YS contributed equally to the manuscript
- Received October 3, 2013.
- Accepted January 2, 2014.
- © 2014 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.