Metabolite profiling of mice under long-term fructose drinking and vitamin D deficiency: increased risks for metabolic s
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ORIGINAL ARTICLE
Metabolite profiling of mice under long-term fructose drinking and vitamin D deficiency: increased risks for metabolic syndrome and nonalcoholic fatty liver disease Wenwen Li 1,2 & Li Zhang 3 & Yuanling Liu 2,3 & Chunyan Wang 2,3 & Yijing Long 2,3 & Zhixin Huang 3 & Yuanping Han 3 & Yixiang Duan 2,3 Received: 10 July 2019 / Accepted: 12 August 2020 # University of Navarra 2020
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. Keywords Metabolic syndrome . Nonalcoholic fatty liver disease . Metabolomics . Fructose . Vitamin D deficiency
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. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13105-020-00764-y) contains supplementary material, which is available to authorized users. * Yuanping Han [email protected] * Yixiang Duan [email protected] 1
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
2
Research Center of Analytical Instrumentation, Sichuan University, Chengdu, China
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
Introduction Metabolic syndrome (MetS) is a cluster of metabolic
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