RESUMO
Neurosecretory protein GL (NPGL) is a small secretory protein identified in the hypothalamus of birds and mammals. We recently reported that NPGL exerts obesogenic effects in obesity-prone C57BL6/J mice. However, whether NPGL elicits adiposity in different mouse strains is poorly understood. In this study, we generated transgenic mice overexpressing Npgl using the ICR strain (Npgl Tg mice) to elucidate the obesogenic effects of NPGL in different strains. Npgl Tg mice showed increased white adipose tissue (WAT) mass. Although the mass of brown adipose tissue (BAT) was slightly altered in Npgl Tg mice, hypertrophy of lipid droplets was also observed in BAT. In contrast, fat accumulation was not induced in the liver, with the upregulation of mRNAs related to hepatic lipolysis. These results support the hypothesis that NPGL causes obesity in several strains and species. This report highlights the pivotal role of NPGL in fat accumulation in adipose tissues and contributes to the elucidation of the biological mechanisms underlying obesity and metabolic diseases in heterogeneous populations.
Assuntos
Hipotálamo , Proteínas do Tecido Nervoso , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Dieta Hiperlipídica , Hipotálamo/metabolismo , Masculino , Mamíferos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Proteínas do Tecido Nervoso/metabolismo , Obesidade/genética , Obesidade/metabolismoRESUMO
Recently, we discovered a novel cDNA encoding the precursor of a small secretory protein, neurosecretory protein GL (NPGL), in the chicken mediobasal hypothalamus. In this study, immunohistochemical analysis revealed that NPGL was produced in the infundibular and medial mammillary nuclei of the mediobasal hypothalamus, with immunoreactive fibers also detected in the hypothalamus and the median eminence. As it is known that these regions are involved in feeding behavior in chicks, we surveyed the effects of chronic intracerebroventricular infusion of NPGL on feeding behavior and body mass for a period of two weeks. NPGL stimulated food and water intake, with a concomitant increase in body mass. However, NPGL did not influence mRNA expression of several hypothalamic ingestion-related neuropeptides. Our data suggest that NPGL may be a novel neuronal regulator involved in growth processes in chicks.
Assuntos
Peso Corporal , Galinhas/metabolismo , Ingestão de Líquidos , Comportamento Alimentar/fisiologia , Infusões Intraventriculares , Proteínas do Tecido Nervoso/administração & dosagem , Proteínas do Tecido Nervoso/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , DNA Complementar/metabolismo , Ingestão de Líquidos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
We have recently identified from the avian hypothalamus a complementary DNA encoding a small secretory protein termed neurosecretory protein GL (NPGL). In chicks, NPGL increases body weight gain without affecting food intake. A database search reveals that NPGL is conserved throughout vertebrates. However, the central distribution and functional role of NPGL remains to be elucidated in mammals. In this study, we identified the precursor complementary DNA encoding NPGL from the mouse hypothalamus. Quantitative reverse transcription polymerase chain reaction and morphological analyses revealed that NPGL precursor messenger RNA is robustly expressed in the mediobasal hypothalamus with NPGL neurons specifically localized to the lateroposterior part of the arcuate nucleus in the hypothalamus. NPGL-immunoreactive fibers were observed in close anatomical contact with pro-opiomelanocortin neurons in the rostral region of the arcuate nucleus. NPGL messenger RNA expression was elevated by 24-hour fasting and reduced by feeding of a high-fat diet for 5 weeks. Furthermore, intracerebroventricular injection of mature NPGL increased food intake, pointing to an important role in feeding. Taken together, these findings report on the distribution of NPGL in the mammalian brain and point to an important role for this neuropeptide in energy homeostasis.