《《Limitations in anti-obesity drug development the critical role of hunger-promoting neurons》.pdf

REVIEWS Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons 1,2 1 Marcelo O. Dietrich and Tamas L. Horvath Abstract | Current anti-obesity drugs aim to reduce food intake by either curbing appetite or suppressing the craving for food. However, many of these agents have been associated with severe psychiatric and/or cardiovascular side effects, highlighting the need for alternative therapeutic strategies. Emerging knowledge on the role of the hypothalamus in enabling the central nervous system to adapt to the changing environment — by managing peripheral tissue output and by regulating higher brain functions — may facilitate the discovery of new agents that are more effective and have an acceptable benefit–risk profile. Targeting the molecular pathways that mediate the beneficial effects of calorie restriction and exercise may represent an alternative therapeutic approach for the treatment of chronic metabolic disorders such as obesity. Overnutrition The availability of nutrients (energy) to fuel biological side effects that preclude their long-term use in patients A positive energy balance in reactions is fundamental for life, but continuous over­ (TABLE 1). The number and diversity of these