Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats: vanillin and 4-hydroxybenzaldehyde are the bioactive candidates

Insulin resistance is a common symptom of metabolic diseases such as obesity, type 2 diabetes and hyperlipidemia. We investigated whether Gastrodia elata Blume water extract(GEB), containing phenolic compounds, had a beneficial action on insulin resistance in male Sprague-Dawley rats fed a high fat diet(HFD) and determined how this effect was produced. In addition, the bioactive candidates involved were identified. Rats fed HFD were daily administered with 0.3 g GEB(GEB-L), 1 g GEB(GEB-H), or 1 g cellulose(control) per kg body weight for 8 weeks, while rats in the fourth group were fed a low fat diet(LFD). In vitro study, 4 major components of GEB were tested for their impact on fat accumulation. Rats in the control group exhibited a higher weight gain of epididymal and retroperitoneal fat pads than those fed LFD, while GEB prevented such an increment in a dose-dependent manner. GEB-H significantly decreased energy intake partly through potentiating STAT3 phosphorylation and attenuating AMPK phosphorylation in the hypothalamus. GEB-H also increased energy expenditure with the increase in fat oxidation. GEB-H increased whole body glucose disposal rates and decreased hepatic glucose output compared to the control. Among the major components of GEB, 4-hydroxybenzaldehyde and vanillin decreased triglyceride accumulation by modulating the expression of genes involved in fat metabolism in 3T3-L1 adipocytes. They increased insulin-stimulated glucose uptake to reduce insulin resistance. GEB-H, mainly as a result of the action of 4-hydroxybenzaldehyde and vanillin, reduces insulin resistance by decreasing fat accumulation in adipocytes by activating fat oxidation and potentiating leptin signaling in diet-induced obese rats.