Effects of aging and caloric restriction on brainstem satiety center signals in rats
- 作者：Emmanuel Moysea ; b ; c ; emmanuel.moyse@univ-tours.fr ; emmanuel.moyse@tours.inra.fr ; Karine Bé ; darda ; Sté ; phanie Segurab ; c ; Sté ; phanie Mahautb ; c ; Catherine Tardivelb ; c ; Guylaine Ferlandd ; e ; Bruno Lebrunb ; c ; Pierrette Gaudreaua ; f
- 关键词：Leptin ; BDNF ; Cytokine signaling ; Autonomic nervous system ; Dorsal vagal complex
- 刊名：Mechanisms of Ageing and Development
- 出版年：2012
- 期刊代码：193_00476374
- 类别：med
- 出版时间：February-March, 2012
- 卷：133
- 期：2-3
- 页码：83-91
- 文件大小：1099 K
摘要
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.