Hypothalamic leptin resistance is associated with impaired leptin signal transduction in aged obese rats
Section snippets
Animals
Six- and 24-month-old, male, F344×Brown Norway rats were obtained from Harlan Sprague–Dawley (Indianapolis, IN, USA). Upon arrival, rats were examined and remained in quarantine for 1 week. Animals were cared for in accordance with the principles of the Guide to the Care and Use of Experimental Animals. All efforts were made to minimize the number of animals used and their suffering. Rats were housed individually in micro-isolated cages with a 12:12-h light:dark cycle (07.00 to 19.00 h) and
Dose–response phosphorylation of STAT3 in young and old rats
The tyrosine phosphorylation of STAT3 following i.c.v. leptin administration was determined in hypothalamic lysates by specific immunoreactivity of P-STAT3. In our previous study, we determined that following an i.v. bolus of leptin, maximal levels of P-STAT3 were achieved 1 h post injection (Scarpace et al., 2000b). Similarly, in the present study, following administration of 15 μg leptin, i.c.v., levels of P-STAT3 were greater at 60 min compared with 30 min post injection (data not shown). To
Discussion
The leptin receptor, a member of the class I cytokine receptor family (Tarttaglia, 1997), has signal transduction properties that involve members of the JAK family of enzymes and the STAT proteins. Ligand binding initiates a sequence of events that involves receptor dimerization, JAK autophosphorylation and activation, JAK-mediated receptor phosphorylation, and JAK-mediated tyrosine phosphorylation of STAT3 protein. Subsequently, P-STAT3 proteins dimerize, bind to specific DNA sequences, and
Acknowledgements
Supported by the Medical Research Service of the Department of Veterans Affairs and National Institute on Aging Grant AG-11465.
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