RESUMO
The Lou/C rat, an inbred strain of Wistar origin, was described as a model of resistance to age- and diet-induced obesity. Although such a resistance involves many metabolic parameters described in our previous studies, Lou/C rats also exhibit a spontaneous food restriction due to decreased food consumption during the nocturnal period. We then attempted to delineate the leptin sensitivity and mechanisms implicated in this strain, using different protocols of acute central and peripheral leptin administration. A first analysis of the meal patterns revealed that Lou/C rats eat smaller meals, without any change in meal number compared to age-matched Wistar animals. Although the expression of the recognized leptin transporters (leptin receptors and megalin) measured in the choroid plexus was normal in Lou/C rats, the decreased triglyceridemia observed in these animals is compatible with an increased leptin transport across the blood brain barrier. Improved hypothalamic leptin signaling in Lou/C rats was also suggested by the higher pSTAT3/STAT3 (signal transducer and activator of transcription 3) ratio observed following acute peripheral leptin administration, as well as by the lower hypothalamic mRNA expression of the suppressor of cytokine signaling 3 (SOCS3), known to downregulate leptin signaling. To conclude, spontaneous hypophagia of Lou/C rats appears to be related to improved leptin sensitivity. The main mechanism underlying such a phenomenon consists in improved leptin signaling through the Ob-Rb leptin receptor isoform, which seems to consequently lead to overexpression of brain-derived neurotrophic factor (BDNF) and thyrotropin-releasing hormone (TRH).
Assuntos
Ingestão de Alimentos , Leptina/metabolismo , Obesidade/metabolismo , Animais , Hipotálamo/metabolismo , Masculino , Obesidade/genética , Obesidade/fisiopatologia , RNA Mensageiro/genética , Ratos , Ratos Wistar , Receptores para Leptina/metabolismo , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/genéticaRESUMO
Cocaine- and amphetamine-regulated transcript (CART) is widely expressed in the brain and various endocrine tissues. CART is implicated in many physiological functions including food intake, drug reward, stress and nociception. No CART receptor has been identified yet. We fused CART(55-102) to the green fluorescent protein (GFP) and found that the ligand suppresses significantly food intake after intracerebroventricular (i.c.v.) injection in mice. Using this ligand, we show specific CART binding sites on HepG2 cells and hypothalamic dissociated cells. In brain sections, CART displaceable binding sites were observed on cell bodies mainly localized in hypothalamic periventricular areas.