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Am J Physiol Endocrinol Metab 282: E312-E317, 2002; doi:10.1152/ajpendo.00037.2001
0193-1849/02 $5.00
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Vol. 282, Issue 2, E312-E317, February 2002

Accelerated substrate cycling: a new energy-wasting role for leptin in vivo

Shannon P. Reidy and Jean-Michel Weber

Biology Department, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5

Simultaneous lipolysis and reesterification form the triacylglycerol/fatty acid (TAG/FA) cycle, a substrate cycle commonly used for thermogenesis. Its rate was measured in vivo by indirect calorimetry and continuous infusion of [2-3H]glycerol and [1-14C]palmitate, after injection of leptin or vehicle saline in rabbits. Leptin stimulated in vivo lipolysis from 9.66 ± 0.62 to 14.78 ± 0.93 µmol · kg-1 · min-1, the rate of appearance of FA from 20.69 ± 2.14 to 29.03 ± 3.03 µmol · kg-1 · min-1, and TAG/FA cycling from 24.82 ± 1.73 to 37.09 ± 2.49 µmol FA · kg-1 · min-1. This large increase in total cycling was caused by an 85% rise in primary cycling (reesterification without transit in the circulation) and accounted for 14% of the difference in metabolic rate between the controls and the leptin-treated animals. This study shows that leptin causes a strong activation of TAG/FA cycling, lipolysis, and FA oxidation, shifting fuel preference from carbohydrates to lipids. Therefore, the acceleration of substrate cycling is a new mechanism triggered by leptin to increase metabolic rate, besides the known induction of uncoupling proteins.

futile cycling; energy expenditure; lipid reserve homeostasis; body weight regulation; obesity


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