科研之友
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摘要
Obesity is one of the leading preventable causes of death worldwide. In its epidemic it is of increasing interest for the pharmaceutical industry to develop drugs that reduce appetite. By reducing appetite overall energy consumption is also reduced. The idea is simple; however, the hormonal system and mechanisms regulating energy intake are extremely complex and therefore drug development is not straightforward. Throughout the central nervous system (CNS), central and peripheral hormones are involved in food intake and body weight balance. They are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis of both cognitive inputs and diverse humoral and neuronal signals of nutritional status. Several peptides and hormones such as: neuropeptide Y (NPY), melanocortins, cocaine and amphetamine-regulated transcript (CART), peptide YY (PYY), pancreatic polypeptide (PP), cholecystokinin (CCK), oxyntomodulin (OXM), glucagon-like peptide 1 (GLP-1), glucose-dependant insulinotropic hormone (GIP), bombesin, leptin and one of the latest discovered and not yet well known - ghrelin, have all revealed an important role in short-and long-term regulation of food intake. This review summarizes the complexity of factors involved in the regulation of appetite and food intake in different areas of the brain, especially in the hypothalamus, and the relationships between the central and peripheral peptides and hormones involved, with emphasis on ghrelin and its receptor together with their potential role as targets for treatment of obesity. The ghrelin receptor originally received considerable attention from pharmaceutical companies because of its prominent role in the release of growth hormone. However, the discovery of the orexigenic properties of ghrelin turned the ghrelin receptor (ghrR) into a target for anti-obesity drugs.
- 出版日期2011
