oa Editorial [ Hot Topic:The Medicinal Chemistry of New Agents to Treat Diabetes and Obesity (Guest Editor: Jie-Fei Cheng)]

Obesity is an extremely common negative physical condition which has an increasing incidence in developed and some developing countries. It means that the accumulation of excessive body fat has become a threat to one 's health. Obesity is dangerous for it is closely associated with a number of terrible diseases, primarily known as type 2 diabetes, bilary, cardiovascular diseases and metabolic syndrome. According to statistics published in 2007 by The Centers for Disease Control and Prevention, 34% of U.S. adults ages 20 and over are suffering from obesity. With the rapidly growing health-care expenditure spent on obesity related diseases, it has become an urgent social problem. Typical primary treatments of obesity are reducing caloric in-take and increasing physical exercise. Drug therapy is required if this fails to achieve the desired results. In some severe cases, surgery is needed. To date, only two anti-obesity drugs have been approved by the FDA for long-term use, both of which have a list of obvious side-effects. Some other important candidates, i.e. Acomplia, have been canceled mainly for safety considerations. Hence, new therapy targets and screening strategies become the hot, new focus of research for novel anti-obesity drugs with desirable pharmacological profiles and fewer side-effects. This issue of Current Topics in Medicinal Chemistry, dedicated to “The Medicinal Chemistry of New Agents to Treat Diabetes and Obesity,” is aimed at describing and highlighting the state of the art of current research and development in the field of diabetes and obesity. The purpose of our current issue is to address the action mechanisms and applications of important anti-obesity targets. Natural products with anti-diabetic activity are also briefly reviewed. This issue presents reviews from five research groups which are involved in the investigation of anti-obesity agents. Min Zhong starts this issue with a review of the biological rationale of TGR5 as an attractive therapeutic target and summarizes the recent efforts in developing promising TGR5 modulators. TGR5 is a membrane G-protein-coupled protein receptor (GPCR) that responds to bile acids, and its modulators may contribute to the prevention and/or the treatment of obesity, type 2 diabetes and metabolic syndrome. It would be promising to see some preclinical and/or clinical results of potent and selective TGR5 modulators in the future. The second review by Li-Fang Yu et al. focuses on AMP-activated protein kinase (AMPK) and the potency of its direct or indirect activators which lead to a series of positive physical effects to improve metabolic diseases including obesity and type 2 diabetes. Many agents have been identified as direct or indirect activators of AMPK, including biguanides and thiazolidinediones. The major challenge of utilizing AMPK activators as novel agents for the treatment of obesity or type 2 diabetes is avoiding the risk of heart disease or the activation effect in the hypothalamus while keeping the original pharmacological effects.