Bariohay Bruno, Lebrun Bruno, Moyse Emmanuel, Jean André
Laboratoire de Physiologie Neurovégétative, Unité Mixte de Recherche Université Paul Cézanne Aix-Marseille III, France.
Endocrinology. 2005 Dec;146(12):5612-20. doi: 10.1210/en.2005-0419. Epub 2005 Sep 15.
Brain-derived neurotrophic factor (BDNF) has recently been implicated as an anorexigenic factor in the central control of food intake. Previous studies focused on the hypothalamus as a probable site of action for this neurotrophin. It was demonstrated that BDNF is an important downstream effector of melanocortin signaling in the ventromedial hypothalamus. In this study, we addressed whether BDNF can modulate food intake in the hindbrain autonomic integrator of food intake regulation, i.e. the dorsal vagal complex (DVC). To this end, we used two complementary methodological approaches in adult rats. First, we measured the effects of intraparenchymal infusions of exogenous BDNF within the DVC on food intake and body weight. Second, we measured the endogenous BDNF protein content in the DVC and hypothalamus after food deprivation, refeeding, or peripheral treatments by the anorexigenic hormones leptin and cholecystokinin (CCK). BDNF infusion within the DVC induced anorexia and weight loss. In the DVC, BDNF protein content decreased after 48 h food deprivation and increased after refeeding. Acute and repetitive peripheral leptin injections induced an increase of the BDNF protein content within the DVC. Moreover, peripheral CCK treatment induced a transient increase of BDNF protein content first in the DVC (30 min after CCK) and later on in the hypothalamus (2 h after CCK). Taken together, these results strongly support the view that BDNF plays a role as an anorexigenic factor in the DVC. Our data also suggest that BDNF may constitute a common downstream effector of leptin and CCK, possibly involved in their synergistic action.
脑源性神经营养因子（BDNF）最近被认为是食物摄入中枢控制中的一种厌食因子。先前的研究集中在下丘脑，认为这可能是这种神经营养因子的作用位点。研究表明，BDNF是腹内侧下丘脑黑皮质素信号的重要下游效应物。在本研究中，我们探讨了BDNF是否能调节食物摄入调节的后脑自主整合器，即迷走背核复合体（DVC）中的食物摄入。为此，我们在成年大鼠中使用了两种互补的方法。首先，我们测量了向DVC实质内注射外源性BDNF对食物摄入和体重的影响。其次，我们测量了禁食、再喂食或用厌食激素瘦素和胆囊收缩素（CCK）进行外周处理后，DVC和下丘脑中内源性BDNF蛋白的含量。向DVC内注射BDNF会导致厌食和体重减轻。在DVC中，禁食48小时后BDNF蛋白含量降低，再喂食后增加。急性和重复外周注射瘦素会导致DVC内BDNF蛋白含量增加。此外，外周CCK处理首先导致DVC中BDNF蛋白含量短暂增加（CCK注射后30分钟），随后在下丘脑中增加（CCK注射后2小时）。综上所述，这些结果有力地支持了BDNF在DVC中作为厌食因子发挥作用的观点。我们的数据还表明，BDNF可能构成瘦素和CCK的共同下游效应物，可能参与它们的协同作用。
