Hop-derived prenylflavonoid isoxanthohumol suppresses insulin resistance by changing the intestinal microbiota and suppressing chronic inflammation in high fat diet-fed mice

摘要

OBJECTIVE: To assess whether the hop-derived polyphenol isoxanthohumol suppresses insulin resistance by changing the intestinal microbiota. MATERIALS AND METHODS: Male C57BL/6J mice (7 weeks of age) were divided into five groups (n = 9-10): Normal Diet (ND), High Fat Diet (HFD), HFD + low dose isoxanthohumol (0.01%IX), HFD + medium dose isoxanthohumol (0.03% IX), and HFD + high dose isoxanthohumol (0.1% IX). Oral glucose tolerance tests (OGTTs) were performed at 4 and 8 weeks, and insulin tolerance tests (ITTs) were performed at 13 weeks. 16S rRNA gene sequencing analyses revealed the fecal microbiota profiles, and the relative abundance of Akkermansia muciniphila and Clostridium cluster XI was calculated by qRT-PCR. Plasma lipopolysaccharide (LPS) levels were measured by ELISA, and mRNA expression levels of tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in epididymal adipose tissues were measured by qRT-PCR. RESULTS: Isoxanthohumol showed antibacterial activity towards several bacterial species and mitigated impaired glucose tolerance and insulin resistance induced by the HFD in a dose-dependent manner, as shown by OGTTs and ITTs. The concentration of phylum Verrucomicrobia bacteria dramatically increased in the 0.1% IX group, the relative abundance of A. muciniphila increased, and that of Clostridium cluster XI decreased. Moreover, the intake of isoxanthohumol decreased the levels of plasma LPS and mRNA expression of TNF-α and IL-1β in epididymal adipose tissues. CONCLUSIONS: We found that isoxanthohumol can suppress HFD-induced insulin resistance by changing the intestinal microbiota and reducing the expression of inflammation factors.