Effect of Oryzanol and Ferulic Acid on the Glucose Metabolism of Mice Fed with a High-Fat DietMyoung Jin Son, Catherine W. Rico, Seok Hyun Nam, and Mi Young KangAbstract: The effects of oryzanol and ferulic acid on the glucose metabolism of high-fat-fed mice were investigated. Male C57BL/6N mice were randomly divided into 4 groups: NC group fed with normal control diet; HF group fed with high-fat (17%) diet; HF-O group fed with high-fat diet supplemented with 0.5% oryzanol; and HF-FA group fed with high-fat diet supplemented with 0.5% ferulic acid. All animals were allowed free access to the experimental diets and water for 7 wk. At the end of the experimental period, the HF-O and HF-FA groups exhibited significantly lower blood glucose level and glucose-6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities, and higher glycogen and insulin concentrations and glucokinase (GK) activity compared with NC and HF groups. The results of this study illustrate that both oryzanol and ferulic acid could reduce the risk of high-fat diet-induced hyperglycemia via regulation of insulin secretion and hepatic glucose-regulating enzyme activities.Keywords: diabetes, ferulic acid, high-fat-fed mice, hypoglycemic effect, oryzanolIntroductionChronic consumption of a high-fat diet has been associated with the development of obesity and type 2 diabetes mellitus (Hill and others 1992; Bray and others 2004). Scientific studies have shown that excessive intake of dietary fat results in increased body weight and poor glucose regulation (Alsaif and Duwaihy2004; Petro and others 2004; Messier and others 2007). Diabetes is characterized by hyperglycemia that results in the generation of free radicals leading to oxidative stress (West 2000). Due to changes in lifestyle patterns, particularly poor eating habit and sedentary lifestyle, the incidence of diabetes has rapidly increased in epidemic proportions. Around 171 million cases of diabetes worldwide were reported in 2001 and it was projected that by 2030, 366 million people will have diabetes (Wild and others 2004). With this increasing global prevalence of diabetes, the need for therapeutic measures against the disease has become stronger and more urgent. A wide range of oral medicines are currently being used for treating diabetes. However, various adverse effects and high rates of secondary failures have been associated with the available antidiabetic medicines (Inzucchi 2002). Thus, finding natural drugs with hypoglycemic activity has now become the focus of scientists and researchers. At present, there is a considerable public and scientific interest in utilizing phytochemicals for the treatment and prevention of various diseases. Naturally occurring phenolic compounds, such as oryzanol and ferulic acid, are known to have strong antioxidant activities (Wang and others 2002; Srinivasan and others 2007). Oryzanol is a mixture of ferulic acid (4-hydroxy-3-methoxycinnamic acid) esters with phytosterols (Lerma-Garcia and others 2009) and primarily extracted from rice bran. Ferulic acid is commonly found in fruits and vegetables, including banana, broccoli, rice bran, and citrus fruits (Zhao and Moghadasian 2008). Both oryzanol and ferulic acid possess several physiological proper ties, such as reduction of serum cholesterol levels (Wilson and others 2007), inhibition of tumor promotion (Yasukawa and others 1998), and protective action against liver injury (Choti-markorn and Ushio 2008). Oxidative stress is regarded as the key factor in the development of diabetes and its associated health disorders. The high-fat diet fed C 57BL/6 mouse model has long been used by researchers in investigating the pathophysiology of impaired glucose tolerance and type 2 diabetes and for the development of new treatments (Surwit and others 1988; Surwit and other s 1991; Schreyer and others 1998; Winzell and Ahren 2004). Since diabetes is a free radical mediated disease, the strong antioxidant activity of oryzanol and ferulic acid may be useful in preventing the development of diabetic hyperglycemia under a high-fat diet. There are limited reports on the physiological functions of these phenolic compounds in relation to glucose metabolism in animal models. Thus, this study was conducted to investigate the effects of dietary feeding of oryzanol and ferulic acid on the glucose metabolism in high-fat-fed C57BL/6 mice.1. Materials and Methods1.1 Animals and dietsTwenty-four male C57BL/6N mice of 4 wk of age, weighing 12 g, were obtained from Orient Inc. (Seoul, Korea). They were individually housed in stainless steel cages in a room maintained at 25C with 50% relative humidity and 12/12 h light/dark cycle and fed with a pelletized chow diet for 2 wk after arrival. The mice were then randomly divided into 4 dietary groups (n = 6). The 1st and 2nd groups were fed with a normal and high-fat (17%, w/w) diets, respectively, while the other 2 groups were fed with high-fa