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Am J Physiol Endocrinol Metab 277: E544-E550, 1999;
0193-1849/99 $5.00
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Vol. 277, Issue 3, E544-E550, September 1999

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

Robert M. O'Doherty1, Paul R. Anderson1, Allan Z. Zhao2, Karin E. Bornfeldt2, and Christopher B. Newgard1

1 Gifford Laboratories for Diabetes Research and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75235; and 2 Department of Pathology and Pharmacology, University of Washington, Seattle, Washington 98195

The effect of moderate hyperleptinemia (~20 ng/ml) on liver and skeletal muscle glycogen metabolism was examined in Wistar rats. Animals were studied ~90 h after receiving recombinant adenoviruses encoding rat leptin (AdCMV-leptin) or beta -galactosidase (AdCMV-beta Gal). Liver and 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 delivery of a glucose bolus, liver glycogen levels were significantly greater in AdCMV-leptin compared with AdCMV-beta Gal rats (P < 0.05). To investigate the mechanism(s) of these differences, glycogen levels were measured immediately after the cessation of a 3- or 6-h glucose infusion or 3, 6, and 9 h after the cessation of a 6-h glucose infusion. Similar increases 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 activities were unaltered by hyperleptinemia. We conclude that moderate increases in plasma leptin levels decrease liver glycogen degradation during the fed-to-fasted transition.

glucose metabolism; metabolic regulation


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