Dataset Information

Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.

ABSTRACT: Genetics plays a central role in susceptibility to obesity and metabolic diseases. BALB/c mice are known to be resistant to high fat diet (HFD)-induced obesity, however the genetic cause remains unknown. We report that deletion of the innate immunity antibacterial gene Nod2 abolishes this resistance, as Nod2 -/- BALB/c mice developed HFD-dependent obesity and hallmark features of metabolic syndrome. Nod2 -/- HFD mice developed hyperlipidemia, hyperglycemia, glucose intolerance, increased adiposity, and steatosis, with large lipid droplets in their hepatocytes. These changes were accompanied by increased expression of immune genes in adipose tissue and differential expression of genes for lipid metabolism, signaling, stress, transport, cell cycle, and development in both adipose tissue and liver. Nod2 -/- HFD mice exhibited changes in the composition of the gut microbiota and long-term treatment with antibiotics abolished diet-dependent weight gain in Nod2 -/- mice, but not in wild type mice. Furthermore, microbiota from Nod2 -/- HFD mice transferred sensitivity to weight gain, steatosis, and hyperglycemia to wild type germ free mice. In summary, we have identified a novel role for Nod2 in obesity and demonstrate that Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.

SUBMITTER: Rodriguez-Nunez I

PROVIDER: S-EPMC5428441 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.

Rodriguez-Nunez Ivan I Caluag Tiffany T Kirby Kori K Rudick Charles N CN Dziarski Roman R Gupta Dipika D

Scientific reports 20170403 1

Genetics plays a central role in susceptibility to obesity and metabolic diseases. BALB/c mice are known to be resistant to high fat diet (HFD)-induced obesity, however the genetic cause remains unknown. We report that deletion of the innate immunity antibacterial gene Nod2 abolishes this resistance, as Nod2 <sup>-/-</sup> BALB/c mice developed HFD-dependent obesity and hallmark features of metabolic syndrome. Nod2 <sup>-/-</sup> HFD mice developed hyperlipidemia, hyperglycemia, glucose intolera ...[more]

PMID: 28373658

Similar Datasets

Project description:BackgroundAssociations have been made between obesity and reduced intestinal numbers of members of the phylum Bacteroidetes, but there is no direct evidence of the role these bacteria play in obesity. Herein, the effects of Bacteroides uniformis CECT 7771 on obesity-related metabolic and immune alterations have been evaluated.Methods and findingsAdult (6-8 week) male wild-type C57BL-6 mice were fed a standard diet or a high-fat-diet HFD to induce obesity, supplemented or not with B. uniformis CECT 7771 for seven weeks. Animal weight was monitored and histologic, biochemical, immunocompetent cell functions, and features of the faecal microbiota were analysed after intervention. The oral administration of B. uniformis CECT 7771 reduced body weight gain, liver steatosis and liver cholesterol and triglyceride concentrations and increased small adipocyte numbers in HFD-fed mice. The strain also reduced serum cholesterol, triglyceride, glucose, insulin and leptin levels, and improved oral tolerance to glucose in HFD fed mice. The bacterial strain also reduced dietary fat absorption, as indicated by the reduced number of fat micelles detected in enterocytes. Moreover, B. uniformis CECT 7771 improved immune defence mechanisms, impaired in obesity. HFD-induced obesity led to a decrease in TNF-α production by peritoneal macrophages stimulated with LPS, conversely, the administration of B. uniformis CECT 7771 increased TNF-α production and phagocytosis. Administering this strain also increased TNF-α production by dendritic cells (DCs) in response to LPS stimulation, which was significantly reduced by HFD. B. uniformis CECT 7771 also restored the capacity of DCs to induce a T-cell proliferation response, which was impaired in obese mice. HFD induced marked changes in gut microbiota composition, which were partially restored by the intervention.ConclusionsAltogether, the findings indicate that administration of B. uniformis CECT 7771 ameliorates HFD-induced metabolic and immune dysfunction associated with intestinal dysbiosis in obese mice.

Dataset Information

Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.

Publications

Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets