Laboratory of Neuroendocrinology of Aging, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Angus Technopole, Montreal, QC, Canada H1W 4A4.
Mech Ageing Dev. 2012 Feb-Mar;133(2-3):83-91. doi: 10.1016/j.mad.2012.01.004. Epub 2012 Jan 24.
Age-related increases of body weight and adiposity, indicating dysregulation of food intake/energy expenditure, can be prevented in rodents by long-term 40% caloric restriction. The dorsal vagal complex (DVC), the brainstem center mediating the satiety reflex, has recently emerged as a determinant effector of long-term feeding adaptation. To study the effects of aging and caloric restriction on satiety circuits, leptin and brain-derived neurotrophic factor (BDNF) signaling systems were studied in 2- and 19-month-old ad libitum-fed (AL) and 19-month-old calorie-restricted (CR) rats. Age-induced hyperleptinemia in AL rats was correlated with elevated DVC BDNF immunoreactive concentrations and satiety threshold stability, suggesting functional desensitization of the DVC to these signals. To better understand this phenomenon, mRNA levels of receptor and post-receptor signaling effectors were measured by real-time RT-PCR. Aging selectively increased BDNF receptors and suppressor of cytokine signaling-3 (SOCS-3) mRNA levels. Caloric restriction prevented age-related increases of serum leptin, DVC BDNF and SOCS-3 mRNA levels, but not those of BDNF receptors. In CR rats, prevention of leptin resistance-promoting SOCS-3 induction was also observed at the protein level. This study suggests that leptin post-receptor targets and BDNF signaling play a role in the establishment of age-related DVC dysfunction.
随着年龄的增长，体重和肥胖增加，表明食物摄入/能量消耗失调，可以通过长期 40%热量限制来预防啮齿动物的这种情况。背侧迷走神经复合体（DVC），作为介导饱腹感反射的脑干中心，最近已成为长期摄食适应的决定效应器。为了研究衰老和热量限制对饱腹感回路的影响，研究了 2 个月和 19 个月龄自由喂养（AL）和 19 个月龄热量限制（CR）大鼠中的瘦素和脑源性神经营养因子（BDNF）信号系统。AL 大鼠的年龄诱导性高瘦素血症与 DVC BDNF 免疫反应性浓度升高和饱腹感阈值稳定性相关，表明 DVC 对这些信号的功能脱敏。为了更好地理解这种现象，通过实时 RT-PCR 测量了受体和受体后信号效应器的 mRNA 水平。衰老选择性增加了 BDNF 受体和细胞因子信号转导抑制因子-3（SOCS-3）的 mRNA 水平。热量限制可防止与年龄相关的血清瘦素、DVC BDNF 和 SOCS-3 mRNA 水平的增加，但不能防止 BDNF 受体的增加。在 CR 大鼠中，还观察到预防促进瘦素抵抗的 SOCS-3 诱导的作用也发生在蛋白质水平上。这项研究表明，瘦素受体后靶标和 BDNF 信号在建立与年龄相关的 DVC 功能障碍方面发挥作用。
