Rebalancing glucolipid metabolism and gut microbiome dysbiosis by nitrate-dependent alleviation of high-fat diet-induced obesity

被引:25
作者
Ma, Linsha [1 ,2 ,3 ]
Hu, Liang [1 ,4 ]
Jin, Luyuan [1 ]
Wang, Jiangyi [1 ]
Li, Xiangchun [1 ]
Wang, Weili [1 ]
Chang, Shimin [1 ,2 ]
Zhang, Chunmei [1 ]
Wang, Jingsong [1 ,5 ]
Wang, Songlin [1 ,3 ,5 ]
机构
[1] Capital Med Univ, Sch Stomatol, Beijing, Peoples R China
[2] Capital Med Univ, Affiliated Beijing Friendship Hosp, Stomatol Dept, Beijing, Peoples R China
[3] Capital Med Univ, Affiliated Beijing Friendship Hosp, Immunol Res Ctr Oral & Syst Hlth, Beijing, Peoples R China
[4] Beijing Stomatol Hosp, Outpatient Dept Oral & Maxillofacial Surg, Beijing, Peoples R China
[5] Capital Med Univ, Sch Basic Med Sci, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
nitrate; obesity; microbiology; metabolic disorders; NITRITE; PROMOTES;
D O I
10.1136/bmjdrc-2020-001255
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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+NaNO(3)group (water containing 2 mM NaNO(3)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+NaNO(3)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, andRuminococcaceaeabundances were altered, andBacteroidales S24-7andAlistipesabundances were higher in the HFD+NaNO(3)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.
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页数:13
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