title: Systemic Characterization of an Obese Phenotype in the Zucker Rat Model Defining Metabolic Axes of Energy Metabolism and Host-Microbial Interactions.
abstract: 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.
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Jutarop
authors.initials: J
authors.lastname: Phetcharaburanin
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Hannah
authors.initials: H
authors.lastname: Lees
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.|Centre for Digestive and Gut Health, Institute of Global Health Innovation, Imperial College London , London SW7 2AZ, United Kingdom.|School of Biosciences, Cardiff University , Cardiff CF10 3AX, United Kingdom.
authors.forename: Julian R
authors.initials: JR
authors.lastname: Marchesi
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.|Centre for Digestive and Gut Health, Institute of Global Health Innovation, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.|Centre for Digestive and Gut Health, Institute of Global Health Innovation, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.affiliation: Department of General and Visceral, Vascular and Pediatric Surgery, University Hospital of Würzburg , 97080 Würzburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Seyfried
authors.affiliation: Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London , South Kensington, London SW7 2AZ, United Kingdom.|Centre for Digestive and Gut Health, Institute of Global Health Innovation, Imperial College London , London SW7 2AZ, United Kingdom.
authors.forename: Jia V
authors.initials: JV
authors.lastname: Li
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D000069196:Gastrointestinal Microbiome; D009682:Magnetic Resonance Spectroscopy; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D009765:Obesity / Q000378:metabolism* / Q000382:microbiology; D010641:Phenotype; D051381:Rats; D011924:Rats, Zucker
keywords: NMR spectroscopy; Zucker rats; metabolic profiling; metabolomics; metabonomics; obesity