Obesity and associated comorbidities are closely linked to gut microbiota
dysbiosis, energy balance, and chronic
inflammation.
Tangeretin, a key citrus polymethoxylated
flavone (PMF), is abundant in citrus fruits and has preventative and
therapeutic effects for numerous diseases. The current study investigated the effects and possible mechanisms of
tangeretin supplementation in preventing
obesity in high-fat diet (HFD)-fed mice. Treatment of HFD-fed mice with
tangeretin potently ameliorated HFD-induced
body weight,
liver steatosis,
glucose intolerance, and
insulin resistance.
Tangeretin mitigated systemic chronic
inflammation by reducing metabolic
endotoxemia and
inflammation-related gene expression in HFD-fed mice. An increased number of small brown adipocytes possessing multilocular and cytoplasmic lipid droplets and upregulation of thermogenic gene expression were observed after
tangeretin treatment.
16S rRNA amplicon sequencing indicated that
tangeretin markedly altered the gut microbiota composition (richness and diversity) and reversed 16 operational taxonomic units (OTUs) back to levels seen in mice consuming a normal chow diet (NCD). Notably,
tangeretin decreased the ratio of Firmicutes-to-Bacteroidetes and greatly enriched Bacteroides and Lactobacillus. Overall, our results suggest that long-term supplementation with citrus
tangeretin ameliorates the phenotype of
obesity by improving adipose thermogenesis and reducing systemic
inflammation and gut microbiota
dysbiosis, which provides a good basis for studying the mechanism of
tangeretin's beneficial effects.