Obesity and type-2 diabetes are national and worldwide epidemics. Since currently available anti-obesity and anti-diabetes drugs have limited efficacy as well as safety concerns, identifying new target compounds, particularly with dual properties in controlling both body weight and blood glucose, is a high priority. Recently, we have identified novel functions of ginsenoside Rb1 (Rb1), the most abundant and biologically active compound in ginseng. Ginseng has been used as a traditional crude medicine in Asian countries to restore and enhance well-being without notable toxic side effects for thousands of years, and is one of the best-selling herbal supplements in the United States. Peripheral administration of Rb1 to rats potently suppresses food intake without eliciting signs of toxicity. Chronic treatment with Rb1 significantly reduces food intake and body weight gain in high-fat diet (HFD)-induced obese rats and also significantly decreases fasting blood glucose and improves impaired glucose tolerance to a greater extent than what occurs in pair-fed controls. These results demonstrate potential novel roles for Rb1 as an anti-obesity and anti-hyperglycemic agent. Our central hypothesis is that Rb1 increases leptin sensitivity to maintain body energy and glucose homeostasis, and it is strongly supported by our preliminary data in lean and HFD-induced obese rats. The rationale for the proposed research is that once the particular mechanisms of Rb1 in the regulation of body weight and blood glucose are understood, the newly acquired information will allow rational design of future pre-clinical studies and clinical trials to develop Rb1 as a novel agent for the prevention and treatment of obesity and diabetes. Guided by strong preliminary data, we propose testing this hypothesis by pursuing three specific aims. First, to determine the interaction of Rb1 and leptin in reducing food intake in rats. Second, to identify the mechanisms through which Rb1 improves energy homeostasis in HFD-induced obese rats. Third, to test the hypothesis that Rb1, like leptin, regulates glucose metabolism by increasing insulin sensitivity at peripheral tissues and/or by increasing insulin secretion. The proposed work is innovative because it assesses novel pharmacological functions of Rb1 in the regulation of energy and glucose homeostasis. Successful completion of the proposed research will enhance our understanding of the mechanisms by which Rb1 prevents and treats obesity and associated symptoms of the metabolic syndrome. Given the continuing epidemics of obesity and diabetes, identifying and understanding a novel pharmacological agent, such as Rb1, with the dual properties of controlling body weight and reducing blood glucose, is expected to have a significant public health impact.
The objective of this project is to elucidate the mechanisms by which the compound Rb1 prevents and treats obesity, diabetes and other symptoms of the metabolic syndrome. Given the growing incidence of obesity and diabetes, identifying and understanding a new pharmacological agent, like Rb1, with dual properties of controlling body weight and reducing blood glucose, is expected to have a significant public health impact.
|May, Aaron A; Bedel, Nicholas D; Shen, Ling et al. (2016) Estrogen and insulin transport through the blood-brain barrier. Physiol Behav 163:312-21|
|May, Aaron A; Liu, Min; Woods, Stephen C et al. (2016) CCK increases the transport of insulin into the brain. Physiol Behav 165:392-7|
|Wang, H H; Liu, M; Portincasa, P et al. (2016) Lack of endogenous cholecystokinin promotes cholelithogenesis in mice. Neurogastroenterol Motil 28:364-75|
|Shen, Ling; Haas, Michael; Wang, David Q-H et al. (2015) Ginsenoside Rb1 increases insulin sensitivity by activating AMP-activated protein kinase in male rats. Physiol Rep 3:|
|Shen, Ling; Wang, David Q-H; Lo, Chunmin C et al. (2015) Gut vagal afferents are necessary for the eating-suppressive effect of intraperitoneally administered ginsenoside Rb1 in rats. Physiol Behav 152:62-7|
|de Bari, Ornella; Wang, Tony Y; Liu, Min et al. (2015) Estrogen induces two distinct cholesterol crystallization pathways by activating ERÎ± and GPR30 in female mice. J Lipid Res 56:1691-700|
|Begg, Denovan P; May, Aaron A; Mul, Joram D et al. (2015) Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin. Diabetes 64:2457-66|
|de Bari, Ornella; Wang, Helen H; Portincasa, Piero et al. (2015) The deletion of the estrogen receptor Î± gene reduces susceptibility to estrogen-induced cholesterol cholelithiasis in female mice. Biochim Biophys Acta 1852:2161-9|
|Shen, Ling; Liu, Yin; Wang, David Q H et al. (2014) Estradiol stimulates apolipoprotein A-IV gene expression in the nucleus of the solitary tract through estrogen receptor-Î±. Endocrinology 155:3882-90|
|de Bari, Ornella; Wang, Tony Y; Liu, Min et al. (2014) Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment. Ann Hepatol 13:728-45|
Showing the most recent 10 out of 16 publications