Central infusion of the melanocortin receptor antagonist agouti-related peptide (AgRP(83-132)) prevents cachexia-related symptoms induced by radiation and colon-26 tumors in mice
| Autor: | Margaret Joppa, Kathleen Gogas, Alan C. Foster, Stacy Markison |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Cachexia Physiology Anorexia Biology Adenocarcinoma Biochemistry Cellular and Molecular Neuroscience Eating Mice Endocrinology Melanocortin receptor Central melanocortin system Internal medicine Cell Line Tumor medicine Animals Humans Agouti-Related Protein Wasting Syndrome Mice Inbred BALB C Receptors Melanocortin digestive oral and skin physiology Body Weight medicine.disease Peptide Fragments Radiation Injuries Experimental medicine.anatomical_structure Colonic Neoplasms Lean body mass Intercellular Signaling Peptides and Proteins medicine.symptom Melanocortin Agouti-related peptide hormones hormone substitutes and hormone antagonists |
| Zdroj: | Peptides. 28(3) |
| ISSN: | 0196-9781 |
| Popis: | Cachexia is a clinical wasting syndrome that occurs in multiple disease states, and is associated with anorexia and a progressive loss of body fat and lean mass. The development of new therapeutics for this disorder is needed due to poor efficacy and multiple side effects of current therapies. The pivotal role played by the central melanocortin system in regulating body weight has made this an attractive target for novel cachexia therapies. The mixed melanocortin receptor antagonist AgRP is an endogenous peptide that induces hyperphagia. Here, we used AgRP(83-132) to investigate the ability of melanocortin antagonism to protect against clinical features of cachexia in two distinct animal models. In an acute model, food intake and body weight gain were reduced in mice exposed to radiation (300 RAD), and delivery of AgRP(83-132) into the lateral cerebral ventricle prevented these effects. In a chronic tumor cachexia model, adult mice were injected subcutaneously with a cell line derived from murine colon-26 adenocarcinoma. Typical of cachexia, tumor-bearing mice progressively reduced body weight and food intake, and gained significantly less muscle mass than controls. Administration of AgRP(83-132) into the lateral ventricles significantly increased body weight and food intake, and changes in muscle mass were similar to the tumor-free control mice. These findings support the idea that antagonism of the central melanocortin system can reduce the negative impact of cachexia and radiation therapy. |
| Databáze: | OpenAIRE |
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