Differential effects of fasting and leptin on proopiomelanocortin peptides in the arcuate nucleus and in the nucleus of the solitary tract
Open Access
- 1 May 2007
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 292 (5), E1348-E1357
- https://doi.org/10.1152/ajpendo.00466.2006
Abstract
The α-melanocyte-stimulating hormone (α-MSH), derived from proopiomelanocortin (POMC), is generated by a posttranslational processing mechanism involving the prohormone convertases (PCs) PC1/3 and PC2. In the brain, α-MSH is produced in the arcuate nucleus (ARC) of the hypothalamus and in the nucleus of the solitary tract (NTS) of the medulla. This peptide is key in controlling energy balance, as judged by changes observed at transcriptional level. However, little information is available regarding the biosynthesis of the precursor POMC and the production of its processed peptides during feeding, fasting, and fasting plus leptin in the ARC compared with the NTS in conjunction with the PC activity. In this study we found that, in the ARC, pomc mRNA, POMC-derived peptides, and PC1/3 all decreased during fasting, and administration of leptin reversed these effects. In contrast, in the NTS, where there is a large amount of a 28.1-kDa peptide similar in size to POMC, the 28.1-kDa peptide and other POMC-derived peptides, including α-MSH, were further accumulated in fasting conditions, whereas pomc mRNA decreased. These changes were not reversed by leptin. We also observed that, during fasting, PC2 levels decreased in the NTS. These data suggest that, in the NTS, fasting induced changes in POMC biosynthesis, and processing is independent of leptin. These observations indicate that changes in energy status affect POMC in the brain in a tissue-specific manner. This represents a novel aspect in the regulation of energy balance and may have implications in the pathophysiology of obesity.Keywords
This publication has 55 references indexed in Scilit:
- The role of the central melanocortin system in the regulation of food intake and energy homeostasis: lessons from mouse modelsPhilosophical Transactions Of The Royal Society B-Biological Sciences, 2006
- Brain stem melanocortinergic modulation of meal size and identification of hypothalamic POMC projectionsAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2005
- Role of Hypothalamic Melanocortin 3/4-Receptors in Mediating Chronic Cardiovascular, Renal, and Metabolic Actions of LeptinHypertension, 2004
- Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin systemNature Neuroscience, 2004
- The Neuroanatomical Axis for Control of Energy BalanceFrontiers in Neuroendocrinology, 2002
- Changes in Hypothalamic Agouti-Related Protein (AGRP), but not α-MSH or Pro-Opiomelanocortin Concentrations in Dietary-Obese and Food-Restricted RatsBiochemical and Biophysical Research Communications, 1999
- Regulation of Hypothalamic Proopiomelanocortin mRNA by Leptin in ob/ob MiceEndocrinology, 1997
- Proopiomelanocortin Neurons Are Direct Targets for Leptin in the HypothalamusEndocrinology, 1997
- Variants of alpha-melanocyte stimulating hormone in rat brain and pituitary: Evidence that acetylated α-MSH exists only in the intermediate lobe of pituitaryBiochemical and Biophysical Research Communications, 1982
- A reduction in the concentration of immunoreactive corticotropin, malanotropin and lipotropin in the brain of the aging ratBrain Research, 1982