Dataset Information

Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism.

ABSTRACT: Inorganic arsenic (iAs) exposure has been associated to various detrimental effects such as development of metabolic syndrome and type 2 diabetes via oxidative stress and induced prolonged activation of the NRF2 transcription factor. Such effects can be aggravated by poor dietary habits. The role of gut microbiota in promoting metabolic changes in response to arsenic has yet to be precisely defined. To address the complexity of the interactions between diet, NFE2L2/NRF2, and gut microbiota, we studied the chronic effects of iAs exposure in wild-type (WT) and Nrf2^-/- mice fed normal (ND) vs. high-fat diet (HFD), on the gut microbial community in the context of hepatic metabolism. We demonstrate that all treatments and interactions influenced bacteria and metabolic profiles, with dietary differences causing a strong overlap of responses between the datasets. By identifying five metabolites of known microbial origin and following their fate across treatments, we provide examples on how gut microbial products can participate in the development of iAs and HFD-induced metabolic disease. Overall, our results underline the importance of the microbial community in driving gut-liver-cross talk during iAs and HFD exposure.

SUBMITTER: Schiro G

PROVIDER: S-EPMC10540274 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism.

Schiro Gabriele G Liu Pengfei P Dodson Matthew M Zhang Donna D DD Ghishan Fayez K FK Barberán Albert A Kiela Pawel R PR

Frontiers in microbiomes 20221123

Inorganic arsenic (iAs) exposure has been associated to various detrimental effects such as development of metabolic syndrome and type 2 diabetes via oxidative stress and induced prolonged activation of the NRF2 transcription factor. Such effects can be aggravated by poor dietary habits. The role of gut microbiota in promoting metabolic changes in response to arsenic has yet to be precisely defined. To address the complexity of the interactions between diet, <i>NFE2L2</i>/NRF2, and gut microbiot ...[more]

PMID: 37779901

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Project description:INTRODUCTION:High-fat diet (HFD)-induced obesity is accompanied by compromised nitric oxide (NO) signaling and gut microbiome dysregulation. Inorganic dietary nitrate, which acts as a NO donor, exerts beneficial effects on metabolic disorders. Here, we evaluated the effects of dietary nitrate on HFD-induced obesity and provided insights into the underlying mechanism. RESEARCH DESIGN AND METHODS:To investigate the preventive effect of dietary nitrate on HFD-induced obesity, C57BL/6 mice were randomly assigned into four groups (n=10/group), including normal control diet group (normal water and chow diet), HFD group (normal water and HFD), HFD+NaNO3 group (water containing 2 mM NaNO3 and HFD), and HFD+NaCl group (water containing 2 mM NaCl and HFD). During the experiment, body weight was monitored and glucolipid metabolism was evaluated. The mechanism underlying the effects of nitrate on HFD-induced obesity was investigated by the following: the NO3 --NO2 --NO pathway; endothelial NO synthase (eNOS) and cyclic guanosine monophosphate (cGMP) levels; gut microbiota via 16SRNA analysis. RESULTS:Dietary nitrate reduced the body weight gain and lipid accumulation in adipose and liver tissues in HFD-fed mice. Hyperlipidemia and insulin resistance caused by HFD were improved in mice supplemented with nitrate. The level of eNOS was upregulated by nitrate in the serum, liver, and inguinal adipose tissue. Nitrate, nitrite, and cGMP levels were decreased in mice fed on HFD but reversed in the HFD+NaNO3 group. Nitrate also rebalanced the colon microbiota and promoted a normal gut microbiome profile by partially attenuating the impacts of HFD. Bacteroidales S24-7, Alistipes, Lactobacillus, and Ruminococcaceae abundances were altered, and Bacteroidales S24-7 and Alistipes abundances were higher in the HFD+NaNO3 group than that in the HFD group. CONCLUSIONS:Inorganic dietary nitrate alleviated HFD-induced obesity and ameliorated disrupted glucolipid metabolism via NO3 --NO2 --NO pathway activation and gut microbiome modulation.

Dataset Information

Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism.

Publications

Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism.

Similar Datasets

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