Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and high-fat diet-induced obese mouse model and affects hepatic transcriptome and gut microbiota profiles.

ABSTRACT

Obesity, the excessive accumulation of lipids in the body, is closely associated with many prevalent human disorders. Continued efforts to identify plant extracts that exhibit anti-obesity effects have drawn much attention. This study investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity activity and how PTE may affect liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet-induced obese mouse model to determine the effects of PTE on lipid accumulation. Next-generation sequencing analysis of liver gene expression and gut microbiota profiles following PTE treatment were conducted to elucidate possible mechanisms. We found that treatment of fully differentiated 3T3-L1 adipocytes with PTE inhibited lipid accumulation in the cells through reducing lipid formation and triglyceride content and by increasing lipase activity. No cytotoxicity was observed from the PTE treatment. After 5 weeks of treatment with PTE, the increased body weight, elevated serum triglyceride content, and liver steatosis in the high-fat diet-induced obese mice were each reduced. Liver transcriptomic analysis revealed that expression of genes involved in lipid and cholesterol metabolism was significantly altered. The low-grade chronic inflammation of obesity caused by a high-fat diet was also decreased after PTE treatment. In addition, treatment with PTE improved the relatively low Bacteroidetes/Firmicutes ratio in the gut of high-fat diet-fed mice through enrichment of the Proteobacteria population and reduction of the Deferribacteres population. In conclusion, treatment with PTE inhibited lipid accumulation by inducing the expression of the master transcription factor PPARα, attenuated the low-grade chronic inflammation of obesity, and also altered gut microbiota profiles. These results indicate that PTE has the potential to be developed into an anti-obesity food supplement and therapy. Abbreviations Abcg5 ATP-binding cassette subfamily G member 5; ALT alanine aminotransferase; AMPK adenosine monophosphate-activated protein kinase; AST aspartate aminotransferase; B/F Bacteroidetes to Firmicutes [ratio]; C/EBPα CCAAT/enhancer-binding protein alpha; CR creatinine; Cyp51 cytochrome P450 family 51; DMEM Dulbecco's modified Eagle's medium; Fabp5 fatty acid-binding protein 5; FBS fetal bovine serum; Fdps farnesyl diphosphate synthase; Glc Glucose; HFD high-fat diet; GO gene ontology; HPRT hypoxanthine guanine phosphoribosyl transferase; IBMS 3-isobutyl-1-methylxanthine; Idi1 isopentenyl-diphosphate delta isomerase 1; IL-1ß interleukin-1-beta; Lpin1 phosphatidic acid phosphohydrolase; LPS lipopolysaccharide; Mvd mevalonate diphosphate decarboxylase; ND normal diet; OTU operational taxonomic units; Pcsk9 proprotein convertase subtilisin/kexin 9; Pctp phosphatidylcholine transfer protein; PPARα peroxisome proliferator-activated receptor alpha; PPARγ peroxisome proliferator-activated receptor gamma; PTE Polygala tenuifolia extract; Saa1 serum amyloid A1; SD standard deviation; SEM standard error of the mean; Serpina12 serpin family member 12; Sqle squalene monooxygenase; SREBP1C sterol regulatory element-binding protein 1C; TCHO total cholesterol; TG triglyceride.