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Antioxidant Drug Ternpol Promotes Functional Metabolic Changes in the Gut Microbiota
Cai, Jingwei1; Zhang, Limin1,2; Jones, Richard A.1; Correll, Jared B.1; Hatzakis, Emmanuel4; Smith, Philip B.3; Gonzalez, Frank J.5; Patterson, Andrew D.1
AbstractRecent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver H-1 NMR-based metabolomics identified a dose dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum H-1 NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state.
KeywordScfas Metabolomics Gc-ms Nmr Bomb Calorimetry Tempol Obesity
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemical Research Methods
WOS IDWOS:000369771700020
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Document Type期刊论文
Affiliation1.Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, State Coll, PA 16802 USA
2.Chinese Acad Sci, Wuhan Inst Phys & Math, Natl Ctr Magnet Resonance Wuhan, CAS Key Lab Magnet Resonance Biol Syst,State Key, Wuhan 430071, Peoples R China
3.Penn State Univ, Metabol Facil, Huck Inst Life Sci, State Coll, PA 16802 USA
4.Penn State Univ, Dept Chem, State Coll, PA 16802 USA
5.NCI, Lab Metab, NIH, Bethesda, MD 20892 USA
Recommended Citation
GB/T 7714
Cai, Jingwei,Zhang, Limin,Jones, Richard A.,et al. Antioxidant Drug Ternpol Promotes Functional Metabolic Changes in the Gut Microbiota[J]. JOURNAL OF PROTEOME RESEARCH,2016,15(2):563-571.
APA Cai, Jingwei.,Zhang, Limin.,Jones, Richard A..,Correll, Jared B..,Hatzakis, Emmanuel.,...&Patterson, Andrew D..(2016).Antioxidant Drug Ternpol Promotes Functional Metabolic Changes in the Gut Microbiota.JOURNAL OF PROTEOME RESEARCH,15(2),563-571.
MLA Cai, Jingwei,et al."Antioxidant Drug Ternpol Promotes Functional Metabolic Changes in the Gut Microbiota".JOURNAL OF PROTEOME RESEARCH 15.2(2016):563-571.
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