Article Text
Abstract
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.
- nitrate
- obesity
- microbiology
- metabolic disorders
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Footnotes
Contributors SW designed the experiment. LM performed most of the experiment. LH, LJ, JiaW, XL, WW, and SC contributed to the samples and data collection. Data were analyzed by LM, LH, and SW. LM and SW wrote this manuscript.
Funding This study was supported by grants from the National Natural Science Foundation of China (91649124; 81400527 to SW); the 2016 QNRC001 Young Elite Scientist Sponsorship Program by CAST (2016 QNRC001); Chinese Academy of Medical Sciences (CAMS Innovation Fund for Medical Sciences 2019-12M-5-031); Beijing Municipal Science & Technology Commission No. Z181100001718208; Beijing Municipal Education Commission No. 119207020201; Beijing Municipality Government grants (Beijing Scholar Program- PXM2018_014226_000021; PXM2018_193312_000006_0028S643_FCG; PXM2017_014226_000023; SML20151401).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The current study was approved by the Animal Care and Use Committee of Capital Medical University (approval no. AEEI-2016-064). There was no human experiment in the study and patient informed consent was not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information.