Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

摘要: 7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against variety of pathologies. Chronic administration DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have elucidated. We discovered oral supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation female In contrast, male mice were protected from adiposity, had paradoxical worsening accumulation upon supplementation. Consistent with these sexually dimorphic effects on body weight metabolic health, 7,8-DHF induced early stable remodeling intestinal microbiome. increased gut microbial diversity, suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory positively associated inflammation. Changes microbiome preceded alterations weights, silico analyses indicated changes highly predictive subsequent gain While some also observed DHF-supplemented mice, distinct those females and, importantly, animals. The temporality preceding suggests role for mediating weight. Given significant clinical interest across wide range pathologies, further elucidation will aid development effective therapies.