Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats. Export

@article{ Leptin signal transduction; STAT3; Oxygen consumption; Aging, abstract = {The purpose of this study was to determine if long-term leptin treatment desensitizes leptin signal transduction and the subsequent downstream anorexic and thermogenic responses in normal and leptin-resistant age-related obese rats. To this end, we administered, i.c.v., recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or control virus into young and aged-obese rats and after 9 or 46 days, examined food intake, oxygen consumption, body weight, serum leptin, STAT3 phosphorylation, hypothalamic NPY and POMC mRNAs, and UCP1 expression and protein level in brown adipose tissue (BAT). In young rats, rAAV-leptin depleted body fat and both anorexic and thermogenic mechanisms contributed to this effect. Moreover, leptin signal transduction was not desensitized, and there were persistent physiological responses. Similarly, in the aged-obese rats, there was unabated leptin signal transduction, however, both the anorexic and thermogenic responses completely attenuated sometime after day 9. This attenuation, downstream of the leptin receptor, may be contributing to the leptin-resistance and age-related weight gain in these aged-obese rats. Finally, in young rats, although the initial responses to rAAV-leptin were dominated by anorexic responses, by 46 days, the predominant response was thermogenic rather than anorexic, suggesting that energy expenditure may be an important component of long-term weight maintenance.}, address = {Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida 32608-1197, USA. scarpace@ufl.edu}, author = {Scarpace, P. J. and Matheny, M. and Zhang, Y. and T\"{u}mer, N. and Frase, C. D. and Shek, E. W. and Hong, B. and Prima, V. and Zolotukhin, S.}, citeulike-article-id = {3089751}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11955525}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11955525}, citeulike-linkout-2 = {http://diabetes.diabetesjournals.org/cgi/content/full/57/3/614}, issn = {0028-3908}, journal = {Neuropharmacology}, keywords = {and, brain, in, leptin, obese, prevention, treatment}, month = {March}, number = {4}, pages = {548--561}, posted-at = {2008-08-06 00:22:19}, priority = {5}, title = {Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11955525}, volume = {42}, year = {2002} }

TY - JOUR ID - Leptin signal transduction; STAT3; Oxygen consumption; Aging L3 - citeulike-article-id:3089751 N2 - The purpose of this study was to determine if long-term leptin treatment desensitizes leptin signal transduction and the subsequent downstream anorexic and thermogenic responses in normal and leptin-resistant age-related obese rats. To this end, we administered, i.c.v., recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or control virus into young and aged-obese rats and after 9 or 46 days, examined food intake, oxygen consumption, body weight, serum leptin, STAT3 phosphorylation, hypothalamic NPY and POMC mRNAs, and UCP1 expression and protein level in brown adipose tissue (BAT). In young rats, rAAV-leptin depleted body fat and both anorexic and thermogenic mechanisms contributed to this effect. Moreover, leptin signal transduction was not desensitized, and there were persistent physiological responses. Similarly, in the aged-obese rats, there was unabated leptin signal transduction, however, both the anorexic and thermogenic responses completely attenuated sometime after day 9. This attenuation, downstream of the leptin receptor, may be contributing to the leptin-resistance and age-related weight gain in these aged-obese rats. Finally, in young rats, although the initial responses to rAAV-leptin were dominated by anorexic responses, by 46 days, the predominant response was thermogenic rather than anorexic, suggesting that energy expenditure may be an important component of long-term weight maintenance. IS - 4 JF - Neuropharmacology SN - 0028-3908 AD - Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida 32608-1197, USA. scarpace@ufl.edu EP - 561 TI - Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats. VL - 42 SP - 548 KW - and KW - brain KW - in KW - leptin KW - obese KW - prevention KW - treatment AU - Scarpace, PJ AU - Matheny, M AU - Zhang, Y AU - Tümer, N AU - Frase, CD AU - Shek, EW AU - Hong, B AU - Prima, V AU - Zolotukhin, S PY - 2002/03// UR - http://view.ncbi.nlm.nih.gov/pubmed/11955525 ER -