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The metabolic response to a high-fat diet reveals obesity-prone and -resistant phenotypes in mice with distinct mRNA-seq transcriptome profiles

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Abstract

Objectives:

The aim of this study was to explore the phenotypic differences underpinning obesity susceptibility or resistance based on the metabolic and transcriptional profiling of C57BL/6J mice fed a high-fat diet (HFD).

Methods:

The mice were fed either a normal diet or HFD for 12 weeks. After 6 weeks, the mice on HFD were classified as either obesity-prone (OP) or obesity-resistant (OR) depending on the body weight gain.

Results:

Lipid profiles from plasma and liver significantly improved in OR mice relative to the OP group. Energy expenditure was greater in OR mice than in OP mice, with a simultaneous decrease in body fat mass. Epididymal white adipose tissue (eWAT) and liver were enlarged in OP mice (with visible immune-cell infiltration), but these effects were attenuated in OR mice compared with OP mice. Overall glucose metabolism was enhanced in OR mice compared with OP mice, including homeostasis model assessment for insulin resistance, plasma glucose and insulin concentrations, glucokinase activity and hepatic glycogen. Plasma adipokines and proinflammatory cytokines were upregulated in OP mice, and these changes were attenuated in OR mice. Transcriptomic profiles of eWAT and liver revealed common and divergent patterns of transcriptional changes in OP and OR mice, and pointed to differential metabolic phenotypes of OP and OR mice. There were substantial differences between OP and OR mice in molecular pathways, including atherosclerosis signaling, sperm motility, cAMP-mediated signaling in eWAT; and fibrosis, agranulocyte adhesion and diapedesis, and atherosclerosis signaling in liver.

Conclusions:

Taken altogether, the results provide robust evidence of major divergence in the transcriptomes, phenotypes and metabolic processes between obesity susceptibility and obesity resistance in the HFD-fed C57BL/6J mice.

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Acknowledgements

This work was supported by the Bio-Synergy Research Project (NRF-2012M3A9C4048818) and the Science Research Center Project (NRF-2015R1A5A6001906) of the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea.

Author information

Author notes

  1. J-Y Choi and R A McGregor: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Food Sciences and Nutrition, Kyungpook National University, Daegu, Republic of Korea

    J-Y Choi, E-Y Kwon, Y J Kim, Y Han & M-S Choi

  2. Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu, Republic of Korea

    J-Y Choi & M-S Choi

  3. Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea

    R A McGregor

  4. Department of Food Sciences and Nutrition, Hallym University, Chuncheon, Republic of Korea

    J H Y Park

  5. Department of Food Science and Technology, Seoul National University, Seoul, Republic of Korea

    K W Lee

  6. CHA Cancer Institute, CHA University, Kyunggi-do, Republic of Korea

    S-J Kim & J Kim

  7. Department of Biomedical Sciences, College of Life Sciences, CHA University, Kyunggi-do, Republic of Korea

    S-J Kim

  8. Department of Biotechnology, Daegu University, Kyungsan, Republic of Korea

    J W Yun

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  1. J-Y Choi
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Corresponding author

Correspondence to M-S Choi.

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The authors declare no conflict of interest.

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Author contributions

J-YC performed the experiments, analyzed the data and wrote/edited the manuscript. RAM analyzed the data and wrote the manuscript. E-YK, YJK and YH performed the experiments and reviewed the manuscript. JHYP, KWL, S-JK, JK and JWY designed the study and reviewed the manuscript. M-SC supervised this work and had full access to all the data and therefore takes full responsibility for the integrity of the results and accuracy of the data analysis.

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Choi, JY., McGregor, R., Kwon, EY. et al. The metabolic response to a high-fat diet reveals obesity-prone and -resistant phenotypes in mice with distinct mRNA-seq transcriptome profiles. Int J Obes 40, 1452–1460 (2016). https://doi.org/10.1038/ijo.2016.70

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