Mitochondrial metabolomic profiling for elucidating the alleviating potential of Polygonatum kingianum against high-fat diet-induced nonalcoholic fatty liver disease.

Abstract

BACKGROUNDDeveloping mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represent attractive strategies for therapy of non-alcoholic fatty liver disease (NAFLD). Polygonatum kingianum (PK) has been traditionally used in China as a medicinal and nutritional ingredient for centuries and can alleviate high-fat diet (HFD)-induced NAFLD by promoting mitochondrial functions. To date, the underlying molecular mechanism of PK for treating mitochondrial dysfunctions and thus alleviating NAFLD remains unclear.AIMTo identify the molecular mechanism behind the mitochondrial regulatory action of PK against HFD-induced NAFLD in rats.METHODSNAFLD model was induced in rats with HFD. The rats were intragastrically administered PK (4 g/kg per day) for 14 wk. Metabolites in hepatic mitochondrial samples were profiled through ultra-high performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to find the potential biomarkers and metabolic pathways.RESULTSPK significantly restored the metabolites’ levels in the mitochondrial samples. Ten potential biomarkers were identified in the analyzed samples. These biomarkers are involved in riboflavin metabolism.CONCLUSIONPK can alleviate HFD-induced NAFLD by regulating the riboflavin metabolism and further improving the mitochondrial functions. Thus, PK is a promising mitochondrial regulator/nutrient for alleviating NAFLD-associated diseases.