Sparing effect of leptin on liver glycogen stores in rats during the fed-to-fasted transition

The effect of moderate hyperleptinemia (similar to 20 ng/ml) on liver and s keletal muscle glycogen metabolism was examined in Wistar rats. Animals wer e studied similar to 90 h after receiving recombinant adenoviruses encoding rat leptin (AdCMV-leptin) or beta-galactosidase (AdCMV-beta Gal). Liver an d skeletal muscle glycogen levels in the fed and fasted (18 h) states were similar in AdCMV-leptin- and AdCMV-beta Gal-treated rats. However, after de livery of a glucose bolus, liver glycogen levels were significantly greater in AdCMV-leptin compared with AdCMV-beta Gal rats (P < 0.05). To investiga te the mechanism(s) of these differences, glycogen levels were measured imm ediately after the cessation of a 3- or 6-h glucose infusion or 3, 6, and s imilar to 90 h after the cessation of a 6-h glucose infusion. Similar incre ases in liver and skeletal muscle glycogen occurred in hyperleptinemic and control rats in response to glucose infusions. However, 3 and 6 h after the cessation of a glucose infusion, liver glycogen levels were approximately twofold greater (P < 0.05) in AdCMV-leptin-treated compared with AdCMV-beta Gal-treated animals. Skeletal muscle glycogen levels were similar in AdCMV -leptin-treated and AdCMV-beta Gal-treated animals at the same time points. Glycogen phosphorylase, phosphodiesterase 3B, and glycogen synthase activi ties were unaltered by hyperleptinemia. We conclude that moderate increases in plasma leptin levels decrease liver glycogen degradation during the fed -to-fasted transition.