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 r...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-00484-2 |
| _version_ | 1819040059738816512 |
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| author | Ivan Rodriguez-Nunez Tiffany Caluag Kori Kirby Charles N. Rudick Roman Dziarski Dipika Gupta |
| author_facet | Ivan Rodriguez-Nunez Tiffany Caluag Kori Kirby Charles N. Rudick Roman Dziarski Dipika Gupta |
| author_sort | Ivan Rodriguez-Nunez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T09:03:05Z |
| format | Article |
| id | doaj.art-c00e8f898783402ab063d1e8e5fbaf3f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T09:03:05Z |
| publishDate | 2017-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-c00e8f898783402ab063d1e8e5fbaf3f2022-12-21T19:09:25ZengNature PortfolioScientific Reports2045-23222017-04-017111810.1038/s41598-017-00484-2Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunctionIvan Rodriguez-Nunez0Tiffany Caluag1Kori Kirby2Charles N. Rudick3Roman Dziarski4Dipika Gupta5Indiana University School of Medicine–NorthwestIndiana University School of Medicine–NorthwestIndiana University School of Medicine–NorthwestIndiana University School of Medicine–NorthwestIndiana University School of Medicine–NorthwestIndiana University School of Medicine–NorthwestAbstract 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.https://doi.org/10.1038/s41598-017-00484-2 |
| spellingShingle | Ivan Rodriguez-Nunez Tiffany Caluag Kori Kirby Charles N. Rudick Roman Dziarski Dipika Gupta Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction Scientific Reports |
| title | Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction |
| title_full | Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction |
| title_fullStr | Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction |
| title_full_unstemmed | Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction |
| title_short | Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction |
| title_sort | nod2 and nod2 regulated microbiota protect balb c mice from diet induced obesity and metabolic dysfunction |
| url | https://doi.org/10.1038/s41598-017-00484-2 |
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