Abstract
Obesity is a major health concern that poses significant risks for many other diseases, including diabetes, cardiovascular disease, and cancer. Prevalence of these diseases varies by biological sex. This study utilizes a mouse (C57BL/6J) model of obesity to analyze liver and fecal metabolic profiles at various time points of dietary exposure: 5, 9, and 12 months in control or high fat diet (HFD)-exposed mice. Our study discovered that the female HFD group has a more discernable perturbation and set of significant changes in metabolic profiles than the male HFD group. In the female mice, HFD fecal metabolites including pyruvate, aspartate, and glutamate were lower than control diet-exposed mice after both 9th and 12th month exposure time points, while lactate and alanine were significantly downregulated only at the 12th month. Perturbations of liver metabolic profiles were observed in both male and female HFD groups, compared to controls at the 12th month. Overall, the female HFD group showed higher lactate and glutathione levels compared to controls, while the male HFD group showed higher levels of glutamine and taurine compared to controls. These metabolite-based findings in both fecal and liver samples for a diet-induced effect of obesity may help guide future pioneering discoveries relating to the analysis and prevention of obesity in people, especially for females.
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This study was supported by the 2021 North Carolina Agriculture and Technical State University NCTracs Interdisciplinary Team Award (JH, AMD, BW, SHH), the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant KL2TR002490 (AMD), and the National Science Foundation through Grant 2245530 (BW).
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BW and VJ performed metabolomics experiments and data analysis. BW, VJ, and JH wrote the manuscripts. AO, EC, and AC carried out mice husbandry and physiological experiments. SHH and AMD revised the manuscript. JH, BW, and AMD designed the experiments and provided general project guidance for students. JLG revised the manuscript and supported the graduate student AO to conduct the research.
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Wang, B., Jadhav, V., Odelade, A. et al. High fat diet reveals sex-specific fecal and liver metabolic alterations in C57BL/6J obese mice. Metabolomics 19, 97 (2023). https://doi.org/10.1007/s11306-023-02059-x
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DOI: https://doi.org/10.1007/s11306-023-02059-x