ELEVATED FREE FATTY-ACIDS INDUCE UNCOUPLING PROTEIN-3 EXPRESSION IN MUSCLE - A POTENTIAL EXPLANATION FOR THE EFFECT OF FASTING

The newly described uncoupling protein 3 (UCP3) may make an important contribution to thermogenesis in humans because of its high level of e xpression in skeletal muscle, Contrary to expectations, fasting, a con dition that reduces resting energy expenditure, has been reported to i ncrease UCP3 expression in muscle, We have confirmed that a 10-fold in crease in UCP3 mRNA levels occurs in rat quadriceps muscle between PZ and 24 h of food removal, A less consistent twofold increase in muscle UCP2 mRNA levels was observed in animals fasted for up to 72 h, Admin istration of recombinant leptin to prevent a fall in circulating lepti n levels did not eliminate the fasting-induced increase in quadriceps UCP3 expression. Administration of a high dose of glucocorticoid to fe d animals to mimic the increase in corticosterone induced by fasting d id not reproduce the increase ins UCP3 expression observed in fasted a nimals. HIP contrast, elevation of circulating free fatty acid levels in fed animals Ibg Intralipid plus heparin infusion caused significant -increases in the UCP3/actin mRNA ratio compared with saline-infused f ed controls in both extensor digitorum longus (2.01 +/- 0.34 vs, 0.68 +/- 0.11,P = 0.002) and soleus muscles (0.31 +/- 0.07 vs, 0.09 +/- 0.0 2, P = 0.014). We conclude that free fatty acids are a potential media tor of the increase in muscle UCP3 expression that occurs during fasti ng. This seemingly paradoxical induction of UCP3 may be linked to the use of free fatty acid as a fuel rather than an increased need of the organism its dissipate energy.