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Metabolite profiling of mice under long-term fructose drinking and vitamin D deficiency: increased risks for metabolic syndrome and nonalcoholic fatty liver disease

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Abstract

Chronic fructose consumption and vitamin D deficiency (VDD) diet have been linked to the pandemic of metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD). The metabolic mechanisms remain unclear. This study is to explore metabolic changes of mice fed with high fructose syrup and VDD diet in the biogenesis of MetS and NAFLD. C57BL/6J mice were treated with four conditions for 28 weeks: control (standard chow and sterile water), fructose drinking (FD, standard chow and 20 g/100 mL fructose in drinking water), VDD (standard chow with VD depleted and sterile water), and FD+VDD. Metabolites in the serum and liver of mice were analyzed by gas chromatography-mass spectrometry combined with trimethylsilyl derivatization. The histological results indicated that one-hit from long-term fructose drinking led to mild MetS, and a combination with VDD diet induced hepatic steatosis, inflammatory lesion, and interstitial fibrosis in mice, showing significant nonalcoholic steatohepatitis features. Metabolomics analysis showed significant changes in amino acids and short-chain organic acids in response to fructose drinking. VDD diet led to significant increase of hepatic fatty acids, which was consistent with the hepatic morphology of fat deposition. This work demonstrated a concert effect of FD and VDD in promoting MetS and NAFLD through changing in vivo metabolism and signaling pathways. And metabolomics analysis could provide early warnings for the biogenesis of MetS and NAFLD. Importantly, vitamin D supplementation in the diet can balance the metabolic disorders caused by excessive fructose intake.

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Acknowledgments

We appreciate Mei Luo in the Public Health and Clinical Center of Chengdu for the biochemical analysis of mice.

Funding

This work was supported by the postdoctoral research and development fund project of Sichuan University (2019SCU12012), the Key Research and Development Project from the Department of Science and Technology of Sichuan Province (grant number 2017SZ0013), and National Science Foundation of China (grant number 31571165 and 31771288).

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Authors and Affiliations

  1. West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China

    Wenwen Li

  2. Research Center of Analytical Instrumentation, Sichuan University, Chengdu, China

    Wenwen Li, Yuanling Liu, Chunyan Wang, Yijing Long & Yixiang Duan

  3. Key Laboratory of Bio-resource and Eco-environment, Ministry of Education, The College of Life Sciences, Sichuan University, 29 Wangjiang Road, Chengdu, 610065, Sichuan, China

    Li Zhang, Yuanling Liu, Chunyan Wang, Yijing Long, Zhixin Huang, Yuanping Han & Yixiang Duan

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  1. Wenwen Li
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  2. Li Zhang
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  3. Yuanling Liu
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  6. Zhixin Huang
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Contributions

YXD, YPH, and WWL were involved in the study conception and manuscript drafting. LZ and ZXH developed the mouse model and implemented the histological analysis. WWL, YLL, CYW, and YJL were involved in the sample collection and analysis, and metabolomics analysis. WWL and LZ interpreted the results and revised the manuscript. All the authors have reviewed and approved the final manuscript.

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Correspondence to Yuanping Han or Yixiang Duan.

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Key points

·Metabolic changes indicate early progress of metabolic syndrome.

·Chronic fructose drinking changes metabolite levels in serum and liver.

·Vitamin D deficiency promotes hepatic fat deposition, inflammation, and fibrosis.

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Li, W., Zhang, L., Liu, Y. et al. Metabolite profiling of mice under long-term fructose drinking and vitamin D deficiency: increased risks for metabolic syndrome and nonalcoholic fatty liver disease. J Physiol Biochem 76, 587–598 (2020). https://doi.org/10.1007/s13105-020-00764-y

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  • DOI: https://doi.org/10.1007/s13105-020-00764-y

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