The regulation of feeding and metabolic rate and the prevention of murine cancer cachexia with a small-molecule melanocortin-4 receptor antagonist.
Endocrinology
; 146(6): 2766-73, 2005 Jun.
Article
em En
| MEDLINE
| ID: mdl-15774557
ABSTRACT
Cachexia is metabolic disorder characterized by anorexia, an increased metabolic rate, and loss of lean body mass. It is a relatively common disorder, and is a pathological feature of diseases such as cancer, HIV infection, and renal failure. Recent studies have demonstrated that cachexia brought about by a variety of illnesses can be attenuated or reversed by blocking activation of the melanocortin 4 subtype receptor (MC4-R) within the central nervous system. Although the potential use of central MC4-R antagonists for the treatment of cachexia was supported by these studies, utility was limited by the need to deliver these agents intracerebroventricularly. In the current study, we present a series of experiments demonstrating that peripheral administration of a small molecule MC4-R antagonist can effectively stimulate daytime (satiated) food intake as well as decrease basal metabolic rate in normal animals. Furthermore, this compound attenuated cachexia and preserved lean body mass in a murine cancer model. These data clearly demonstrate the potential of small molecule MC4-R antagonists in the treatment of cachexia and underscore the importance of melanocortin signaling in the development of this metabolic disorder.
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Base de dados:
MEDLINE
Assunto principal:
Caquexia
/
Alfa-MSH
/
Carcinoma Pulmonar de Lewis
/
Receptor Tipo 4 de Melanocortina
/
Neoplasias Pulmonares
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article