Overexpression of muscle uncoupling protein 2 content in human obesity associates with reduced skeletal muscle lipid utilization

Uncoupling proteins (UCP) may influence thermogenesis. Since skeletal muscl e plays an important role in energy homeostasis and substrate oxidation, th is study was undertaken to test the hypotheses that skeletal muscle UCP2 co ntent is altered in obesity and could be linked to basal energy expenditure , insulin sensitivity, or substrate oxidation within skeletal muscle under postabsorptive (fasting) conditions. To examine these possibilities, limb b asal energy expenditure and respiratory quotient (bRQ) were measured in 18 obese nondiabetic (Ob) and lean individuals (L). Total body fat (%) ranged from 11% to 46%, In addition, insulin-stimulated rates of glucose disposal (Rd) were measured under euglycemic hyperinsulinemic conditions. Biopsy of vastus lateralis muscle was used to measure cytochrome c oxidase (COX) enzy me activity and UCP2 content. Whereas low muscle COX activity was found in the Ob compared to L (6.9+/-1.6 vs, 9.6+/-1.2 U/g; P<0.001), skeletal muscl e UCP2 content in Ob was significantly higher than in L (48+/-9 vs. 33+/-12 arbitrary units/g; P<0.05). Moreover, UCP2 content was positively correlat ed with percent of total body fat (r=0.57; P<0.05) and bRQ (r=0.59; P<0.01) , but not with visceral fat (r=0.17; P=0.49), basal energy expenditure (r=0 .07; P=0.79) or Rd (r=-0.23; P=0.34). In summary, these results indicate th at if development of obesity in humans is mediated by defective expression of UCP2 within skeletal muscle, then this effect is not observed in people with established obesity. The present study also suggests that skeletal mus cle UCP2 content is not related to basal energy expenditure or insulin sens itivity in humans, However, the increased content of UCP2 within skeletal m uscle in obesity appears to coincide with a reduced postabsorptive lipid ut ilization by muscle.