Accelerated substrate cycling: a new energy-wasting role for leptin in vivo.
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-(3)H]glycerol and [1-(14)C]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 micromol x kg(-1) x min(-1), the rate of appearance of FA from 20.69 +/- 2.14 to 29.03 +/- 3.03 micromol x kg(-1) x min(-1), and TAG/FA cycling from 24.82 +/- 1.73 to 37.09 +/- 2.49 micromol FA x kg(-1) x 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.
Reidy
Shannon P
SP
Biology Department, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5.
Weber
Jean-Michel
JM
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D007700:Kinetics; D020738:Leptin / Q000097:blood / Q000502:physiology*; D008297:Male; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011817:Rabbits; D015219:Substrate Cycling / Q000502:physiology; D022722:Thermogenesis / Q000502:physiology; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D014280:Triglycerides; D005990:Glycerol