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Obesity and cage environment modulate metabolism in the Zucker rat: a multiple biological matrix approach to characterizing metabolic phenomena

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Title: Obesity and cage environment modulate metabolism in the Zucker rat: a multiple biological matrix approach to characterizing metabolic phenomena
Authors: Lees, HJ
Swann, JR
Poucher, S
Holmes, E
Wilson, ID
Nicholson, JK
Item Type: Journal Article
Abstract: Obesity and its comorbidities are increasing worldwide imposing a heavy socioeconomic burden. The effects of obesity on the metabolic profiles of tissues (liver, kidney, pancreas), urine, and the systemic circulation were investigated in the Zucker rat model using 1H NMR spectroscopy coupled to multivariate statistical analysis. The metabolic profiles of the obese ( fa/ fa) animals were clearly differentiated from the two phenotypically lean phenotypes, ((+/+) and ( fa/+)) within each biological compartment studied, and across all matrices combined. No significant differences were observed between the metabolic profiles of the genotypically distinct lean strains. Obese Zucker rats were characterized by higher relative concentrations of blood lipid species, cross-compartmental amino acids (particularly BCAAs), urinary and liver metabolites relating to the TCA cycle and glucose metabolism; and lower amounts of urinary gut microbial-host cometabolites, and intermatrix metabolites associated with creatine metabolism. Further to this, the obese Zucker rat metabotype was defined by significant metabolic alterations relating to disruptions in the metabolism of choline across all compartments analyzed. The cage environment was found to have a significant effect on urinary metabolites related to gut-microbial metabolism, with additional cage-microenvironment trends also observed in liver, kidney, and pancreas. This study emphasizes the value in metabotyping multiple biological matrices simultaneously to gain a better understanding of systemic perturbations in metabolism, and also underscores the need for control or evaluation of cage environment when designing and interpreting data from metabonomic studies in animal models.
Issue Date: 3-May-2019
Date of Acceptance: 1-Apr-2019
URI: http://hdl.handle.net/10044/1/70039
DOI: https://dx.doi.org/10.1021/acs.jproteome.9b00040
ISSN: 1535-3893
Publisher: American Chemical Society
Start Page: 2160
End Page: 2174
Journal / Book Title: Journal of Proteome Research
Volume: 18
Issue: 5
Copyright Statement: © 2019 American Chemical Society
Keywords: NMR spectroscopy
Zucker rat
cage effect
metabolic profiling
NMR spectroscopy
Zucker rat
cage effect
metabolic profiling
06 Biological Sciences
03 Chemical Sciences
Biochemistry & Molecular Biology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-04-02
Appears in Collections:Department of Surgery and Cancer