Fig. 6: Resveratrol intervention exhibits metabolic beneficial effects on obesogenic diet-challenged Fgf21^fl/fl but not lFgf21^-/- mice.

A Illustration of the animal experimental timeline. B Blood glucose level and AUC during glucose tolerance test of Fgf21^fl/fl and lFgf21^-/- mice. C Fasting glucose level at the end of the study. D Serum Insulin level. E Body weight during the experimental period. F Body weight gain at the end of the 16th week after overnight fasting. G Serum TG level of indicated group of mice. H Hepatic TG content of indicated group of mice. I Diagram shows our view that it is gut microbiome that mediates functions of dietary interventions, involving the hepatic hormone FGF21. Dietary intervention including dietary polyphenol supplementation or dietary behavioral changes alter gut microbiome composition and diversity. This in term triggers organ-organ crosstalk involving the gut-brain, gut-liver or other axis, with altered entero-endocrine hormone (GLP-1, GIP, and others) production and function, and altered levels of gut metabolites (bile acids and others), leading to the alteration on hepatic FGF21 production and sensitivity. Hence, without hepatic FGF21, dietary intervention cannot exert its metabolic beneficial effect. Data are shown as the mean ± SEM (n = 5 for Fgf21^fl/fl, and n = 6 for lFgf21^-/-). *p < 0.05, **p < 0.01 and ****p < 0.0001.