Metabolic syndrome is a chronic metabolic disorder that has turned into a severe health problem worldwide. A previous study reported that large yellow
tea exhibited better anti-diabetic and
lipid-lowering effects than
green tea. Nevertheless, the potential mechanisms are not yet understood. In this study, we examined the prevention effects and mechanisms of large yellow
tea water extract (LWE) on
metabolic syndrome using
leptin receptor knockout (Lepr-/-) rats. Seven-week-old male Lepr-/- and wild type (WT) littermate rats were divided into Lepr-/- control group (KO) (n = 5), Lepr-/- with LWE-treated group (KL) (n = 5), WT control group (WT) (n = 6), and WT with LWE intervention group (WL) (n = 6). Then, the rats were administered water or LWE (700 mg/kg BW) daily by oral gavage for 24 weeks, respectively. The results showed that the administration of LWE significantly reduced the serum concentrations of random
blood glucose, total
cholesterol,
triglyceride, and
free fatty acids, and increased
glucose tolerance in Lepr-/- rats. Moreover, LWE remarkably reduced hepatic
lipid accumulation and alleviated
fatty liver formation in Lepr-/- rats. A mechanistic study showed that LWE obviously activated SIRT6 and decreased the expression of key lipogenesis-related molecules SREBP1, FAS, and DGAT1 in the livers of Lepr-/- rats. Furthermore, LWE significantly improved microbiota
dysbiosis via an increase in gut microbiota diversity and an abundance of the microbiota that produce
short chain fatty acids (SCFAs), such as Ruminococcaceae, Faecalibaculum, Intestinimonas, and Alistipes. Finally, LWE supplementation increased the concentrations of SCFAs in the feces of Lepr-/- rats. These results revealed that LWE attenuated
metabolic syndrome of Lepr-/- rats via the reduction of hepatic
lipid synthesis through the SIRT6/SREBP1 pathway and the modulation of gut microbiota.