Dietary Bitter Melon Seed Increases Peroxisome Proliferator-Activated Receptor-c Gene Expression in Adipose Tissue, Down-Regulates the Nuclear Factor-jB Expression, and Alleviates the Symptoms Associated with Metabolic Syndrome Vidya Gadang, 1 William Gilbert, 1 Navam Hettiararchchy, 1 Ronny Horax, 1 Laxmansa Katwa, 2 and Latha Devareddy 1 1 Department of Food Science, University of Arkansas, Fayetteville, Arkansas; and 2 Department of Physiology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina, USA ABSTRACT The objective of this study was to examine the extent to which bitter melon seed (BMS) alleviates the symptoms associated with metabolic syndrome and elucidate the mechanism by which BMS exerts beneficial effects. Three- month-old female Zucker rats were assigned to following groups: lean control (L-Ctrl), obese control (O-Ctrl), and obese þ BMS (O-BMS). The control groups were fed AIN-93M purified rodent diet, and the O-BMS group was fed AIN-93M diet modified to contain 3.0% (wt=wt) ground BMS for 100 days. After 100 days of treatment, BMS supplementation in the obese rats lowered the total serum cholesterol by 38% and low-density lipoprotein-cholesterol levels by about 52% and increased the ratio of serum high-density lipoprotein-cholesterol to total cholesterol compared to the O-Ctrl group. The percentage of total liver lipids was about 32% lower and serum triglyceride levels were 71% higher in the O-BMS group compared to the O-Ctrl group. Serum glucose levels were significantly lowered partly because of the increase in the serum insulin levels in the BMS-based diet groups. BMS supplementation increased the expression of peroxisome proliferator- activated receptor-g (PPAR-g) in the white adipose tissue of the obese rats significantly (P < .05) and down-regulated the expression of PPAR-g, nuclear factor-kB (NF-kB), and interferon-g mRNA in heart tissue of the obese rats. The findings of this study suggest that BMS improves the serum and liver lipid profiles and serum glucose levels by modulating PPAR-g gene expression. To our knowledge, this study for the first time shows that BMS exerts cardioprotective effects by down-regulating the NF-kB inflammatory pathway. KEY WORDS:  bitter melon seed  blood lipids  cardiovascular disease  liver lipids INTRODUCTION M etabolic syndrome, a major health problem in the United States, is characterized by central obesity, in- sulin resistance, and elevated blood lipids. Metabolic syn- drome is associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease. 1 Obesity and a sedentary lifestyle are underlying risk factors along this syndrome’s pathway to disease, and therefore changes in living habits are a first-line intervention in the prevention and treatment of diabetes and cardiovascular disease. 2 In addition to increasing physical activity, one of the aspects of lifestyle modification for preventing metabolic syndrome is changes in diet. Foods rich in phytochemicals that possess health benefits such as hypoglycemic and hy- polipidemic effects have become a central focus for research to prevent risk factors associated with metabolic syndrome. Momordica charantia, commonly known as bitter gourd or bitter melon, a commonly consumed vegetable in Asia, has been recognized for its medicinal value. The most note- worthy health benefit of the juice or whole powder of bitter gourd fruit is the hypoglycemic potential both in diabetic rat models and in human subjects with type 2 diabetes. 3–6 The hypoglycemic activity of M. charantia was attributed to a few isolated phytochemicals such as charantin, polypeptide- p, momordin Ic, oleanolic acid 3-O-monodesmoside, and oleanolic acid 3-O-glucuronide. 7–9 In addition, M. charantia has been shown to significantly reduce serum cholesterol and triglycerides in normal rats as well as diabetic rats. 10–13 Dietary bitter melon was shown to suppress inflammatory responses by enhancing the humoral immunity. 14 However, there is a relative paucity of data regarding the molecular mechanisms through which bitter melon exerts its hypo- glycemic and hypolipidemic activity. In recent years numerous efforts have been directed to- ward understanding the molecular mechanisms that govern adipogenesis. Peroxisome proliferator-activated receptor (PPAR)-g, a nuclear receptor, is highly expressed in adipose Manuscript received 13 January 2010. Revision accepted 26 April 2010. Address correspondence to: Dr. Latha Devareddy, Department of Food Science, Uni- versity of Arkansas, Fayetteville, AR 72704, USA, E-mail: ldevared@mail.uark.edu JOURNAL OF MEDICINAL FOOD J Med Food 14 (1/2) 2011, 86–93 # Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition DOI: 10.1089=jmf.2010.0010 86