RESUMEN
Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.
Asunto(s)
Núcleo Arqueado del Hipotálamo/citología , Conducta Alimentaria/fisiología , Regulación de la Expresión Génica/fisiología , Neuronas/metabolismo , Proteínas/metabolismo , Proteína Relacionada con Agouti , Animales , Anorexia/metabolismo , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Recuento de Células/métodos , Toxina Diftérica/farmacología , Ingestión de Alimentos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular , Ratones , Ratones Noqueados , Neuronas/efectos de los fármacos , Neuropéptido Y/genética , Neuropéptido Y/metabolismo , Proopiomelanocortina/deficiencia , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , Proteínas/genética , Factores de Tiempo , beta-Galactosidasa/biosíntesisRESUMEN
Surfactant protein D (SFTPD) belongs to the family of collectins and is part of the innate immune system. Thereby it plays an important role in the defense of various pathogens. Besides it is involved in the development of acute and chronic inflammation of the lung. Levels of SFTPD are elevated in serum and alveolar lavage of asthmatic patients. As SFTPD binds and neutralizes common allergens like house dust mites it is especially important in allergic asthma. Three common amino acid variants have been identified in SFTPD and association of the first variant has been described to severe infection with respiratory syncytial virus. Furthermore the functional impact of all three amino acid variants has been demonstrated. Due to its function SFTPD represents an ideal candidate gene for bronchial asthma and we were interested whether the polymorphisms were in association with asthma in children. The three polymorphisms leading to amino acid exchanges (Met11Thr, Ala160Thr, and Ser270 Thr) were typed by restriction fragment length polymorphisms in 322 asthmatic children and 270 controls. Association analyses were performed by Armitage's trend test. In addition haplotypes were calculated by FASTEHPLUS and FAMHAP. None of the polymorphisms was in association with bronchial asthma. Haplotype analyses revealed four major haplotypes all of which were evenly distributed between the populations. We conclude from our data that functional amino acid variants in SFTPD do not play a major role in the genetic pre-disposition to bronchial asthma in children.