title: Effects of aging and caloric restriction on brainstem satiety center signals in rats.
abstract: 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.
authors.affiliation: Laboratory of Neuroendocrinology of Aging, Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Angus Technopole, Montreal, QC, Canada H1W 4A4. emmanuel.moyse@univ-tours.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Moyse
authors.forename: Karine
authors.initials: K
authors.lastname: Bédard
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Segura
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Mahaut
authors.forename: Catherine
authors.initials: C
authors.lastname: Tardivel
authors.forename: Guylaine
authors.initials: G
authors.lastname: Ferland
authors.forename: Bruno
authors.initials: B
authors.lastname: Lebrun
authors.forename: Pierrette
authors.initials: P
authors.lastname: Gaudreau
mesh_terms: D050154:Adiposity; D000367:Age Factors; D000375:Aging; D000818:Animals; D001835:Body Weight; D001933:Brain Stem / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D031204:Caloric Restriction; D004435:Eating / Q000502:physiology*; D005786:Gene Expression Regulation; D020738:Leptin / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020738:Leptin; D012333:RNA, Messenger; C491408:Socs2 protein, rat; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins