Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metabolism and Host–Microbial Interactions
| Autor: | Jia V. Li, Elaine Holmes, Jutarop Phetcharaburanin, Jeremy K. Nicholson, Julian R. Marchesi, Florian Seyfried, Hannah Lees |
|---|---|
| Přispěvatelé: | AstraZeneca AB, Diabetes Research & Wellness Foundation, Diabetes Research and Wellness Foundation |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
obesity Biochemistry & Molecular Biology medicine.medical_specialty Magnetic Resonance Spectroscopy Phenylalanine 030204 cardiovascular system & hematology Gut flora Biochemistry 03 medical and health sciences chemistry.chemical_compound NMR spectroscopy 0302 clinical medicine Metabolomics Valine Internal medicine medicine Animals Choline metabonomics chemistry.chemical_classification biology metabolic profiling nutritional and metabolic diseases General Chemistry Metabolism 06 Biological Sciences biology.organism_classification Zucker rats metabolomics Gastrointestinal Microbiome Rats Rats Zucker Citric acid cycle Phenotype 030104 developmental biology Endocrinology chemistry Propionate Energy Metabolism 03 Chemical Sciences Metabolic Networks and Pathways |
| Zdroj: | Journal of Proteome Research. 15:1897-1906 |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/acs.jproteome.6b00090 |
| Popis: | The Zucker (fa/fa) rat is a valuable and extensively utilized model for obesity research. However, the metabolic networks underlying the systemic response in the obese Zucker rats remain to be elucidated. This information is important to further our understanding of the circulation of the microbial or host-microbial metabolites and their impact on host metabolism. (1)H nuclear magnetic resonance spectroscopy-based metabolic profiling was used to probe global metabolic differences in portal vein and peripheral blood plasma, urine and fecal water between obese (fa/fa, n = 12) and lean (fa/+, n = 12) Zucker rats. Urinary concentrations of host-microbial co-metabolites were found to be significantly higher in lean Zucker rats. Higher concentrations of fecal lactate, short chain fatty acids (SCFAs), 3-hydroxyphenyl propionic acid and glycerol, and lower levels of valine and glycine were observed in obese rats compared with lean animals. Regardless of phenotype, concentrations of SCFAs, tricarboxylic acid cycle intermediates, and choline metabolites were higher in portal vein blood compared to peripheral blood. However, higher levels of succinate, phenylalanine and tyrosine were observed in portal vein blood compared with peripheral blood from lean rats but not in obese rats. Our findings indicate that the absorption of propionate, acetate, choline, and trimethylamine is independent of the Zucker rat phenotypes. However, urinary host-microbial co-metabolites were highly associated with phenotypes, suggesting distinct gut microbial metabolic activities in lean and obese Zucker rats. This work advances our understanding of metabolic processes associated with obesity, particularly the metabolic functionality of the gut microbiota in the context of obesity. |
| Databáze: | OpenAIRE |
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