This study aims to investigate the potential of virgin grape seed oil (VGSO) to improve insulin resistance and energy metabolism disorder in mice fed a high‐fat diet. The results show that respiratory exchange rate and energy consumption in mice can be increased by the administration of VGSO. Insulin resistance is significantly alleviated by VGSO, which can be attributed to its protective effect on hexokinase and α‐glucosidase activities and improvement in leptin resistance. The effect of refined grape seed oil (RGSO), RGSO reinforced with polyphenol, RGSO reinforced with unsaponifiables, and RGSO reinforced with polyphenol and unsaponifiables on oral glucose tolerance, homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index are determined and compared. The results suggest that polyphenol may be the most critical factor for regulating insulin resistance. Specific linear and polynomial equations are provided to explain the correlation between insulin resistance, energy metabolism, and hyperlipidemia.
Practical Applications: The effects of virgin grape seed oil (VGSO) on insulin resistance and energy metabolism disorder in mice fed a high‐fat diet were investigated. In addition, the key component in VGSO for regulating insulin resistance was preliminarily investigated. Furthermore, the correlations among fasting blood glucose, triglyceride/cholesterol concentration, and respiratory exchange rate/energy consumption/activity level were investigated. This research will provide a theoretical basis for the development of functional edible oil for high blood lipid, cholesterol, and diabetes patients.