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.