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Unique Gut Microbiome Signatures Depict Diet-Versus Genetically Induced Obesity in Mice.

ABSTRACT: The gut microbiome plays an important role in obesity and Type 2 diabetes (T2D); however, it remains unclear whether the gut microbiome could clarify the dietary versus genetic origin of these ailments. Moreover, studies examining the gut microbiome in diet- versus genetically induced obesity/T2D in the same experimental set-up are lacking. We herein characterized the gut microbiomes in three of the most widely used mouse models of obesity/T2D, i.e., genetically induced (leptin-deficient i.e., Lepob/ob; and leptin-receptor-deficient i.e., Lepdb/db) and high-fat diet (HFD)-induced obese (DIO)/T2D mice, with reference to their normal chow-fed (NC) and low-fat-diet-fed (LF) control counterparts. In terms of ?-diversity, Lepob/ob and Lepdb/db mice showed similarity to NC mice, whereas DIO and LF mice appeared as distinct clusters. The phylum- and genus-level compositions were relatively similar in NC, Lepob/ob, and Lepdb/db mice, whereas DIO and LF mice demonstrated distinct compositions. Further analyses revealed several unique bacterial taxa, metagenomic functional features, and their correlation patterns in these models. The data revealed that obesity/T2D driven by diet as opposed to genetics presents distinct gut microbiome signatures enriched with distinct functional capacities, and indicated that these signatures can distinguish diet- versus genetically induced obesity/T2D and, if extrapolated to humans, might offer translational potential in devising dietary and/or genetics-based therapies against these maladies.

SUBMITTER: Nagpal R

PROVIDER: S-EPMC7279357 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Unique Gut Microbiome Signatures Depict Diet-Versus Genetically Induced Obesity in Mice.

Nagpal Ravinder R Mishra Sidharth P SP Yadav Hariom H

International journal of molecular sciences 20200513 10

The gut microbiome plays an important role in obesity and Type 2 diabetes (T2D); however, it remains unclear whether the gut microbiome could clarify the dietary versus genetic origin of these ailments. Moreover, studies examining the gut microbiome in diet- versus genetically induced obesity/T2D in the same experimental set-up are lacking. We herein characterized the gut microbiomes in three of the most widely used mouse models of obesity/T2D, i.e., genetically induced (leptin-deficient i.e., L ...[more]

PMID: 32414080

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Project description:The nitroxide, Tempol, prevents obesity related changes in mice fed a high fat diet (HFD). The purpose of this study was to gain insight into the mechanisms that result in such changes by Tempol in female C3H mice. Microarray methodology, Western blotting, bile acid analyses, and gut microbiome sequencing were used to identify multiple genes, proteins, bile acids, and bacteria that are regulated by Tempol in female C3H mice on HFD. The effects of antibiotics in combination with Tempol on the gut microflora were also studied. Adipose tissue, from Tempol treated mice, was analyzed using targeted gene microarrays revealing up-regulation of fatty acid metabolism genes (Acadm and Acadl > 4-fold, and Acsm3 and Acsm5 > 10-fold). Gene microarray studies of liver tissue from mice switched from HFD to Tempol HFD showed down-regulation of fatty acid synthesis genes and up-regulation of fatty acid oxidation genes. Analyses of proteins involved in obesity revealed that the expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and fasting induced adipose factor/angiopoietin-like protein 4 (FIAF/ANGPTL4) was altered by Tempol HFD. Bile acid studies revealed increases in cholic acid (CA) and deoxycholic acid (DCA) in both the liver and serum of Tempol treated mice. Tempol HFD effect on the gut microbiome composition showed an increase in the population of Akkermansia muciniphila, a bacterial species known to be associated with a lean, anti-inflammatory phenotype. Antibiotic treatment significantly reduced the total level of bacterial numbers, however, Tempol was still effective in reducing the HFD weight gain. Even after antibiotic treatment Tempol still positively influenced several bacterial species such as as Akkermansia muciniphila and Bilophila wadsworthia. The positive effects of Tempol moderating weight gain in female mice fed a HFD involves changes to the gut microbiome, bile acids composition, and finally to changes in genes and proteins involved in fatty acid metabolism and storage.

Dataset Information

Unique Gut Microbiome Signatures Depict Diet-Versus Genetically Induced Obesity in Mice.

Publications

Unique Gut Microbiome Signatures Depict Diet-Versus Genetically Induced Obesity in Mice.

Similar Datasets

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