Decreased uncoupling protein expression and intramyocytic triglyceride depletion in formerly obese subjects.

Objective: To examine the muscular uncoupling protein expression 2 (UCP2) and UCP3 gene expression in morbid obese subjects before and after bariatric surgery [bilio-pancreatic diversion (BPD)].

Research Methods And Procedures: Eleven obese subjects (BMI = 49 +/- 2 kg/m(2)) were studied before BPD and 24 months after BPD. Skeletal muscle UCP2 and UCP3 mRNA was measured using reverse transcriptase-competitive polymerase chain reaction and UCP3 protein by Western blotting. Intramyocytic triglycerides were quantified by high-performance liquid chromatography. Twenty-four-hour energy expenditure and respiratory quotient (RQ) were measured in a respiratory chamber.

Results: After BPD, the average weight loss was approximately 38%. Nonprotein RQ was increased in the postobese subjects (0.73 +/- 0.00 vs. 0.83 +/- 0.02, p < 0.001). The intramyocytic triglyceride level dropped (3.66 +/- 0.16 to 1.60 +/- 0.29 mg/100 mg of fresh tissue, p < 0.0001) after BPD. Expression of UCP2 and UCP3 mRNA was significantly reduced (from 35.9 +/- 6.1% to 18.6 +/- 4.5% of cyclophilin, p = 0.02; from 60.2 +/- 14.0% to 33.4 +/- 8.5%, p = 0.03; respectively). UCP3 protein content was also significantly reduced (272.19 +/- 84.13 vs. 175.78 +/- 60.31, AU, p = 0.04). A multiple regression analysis (R(2) = 0.90) showed that IMTG levels (p = 0.007) represented the most powerful independent variable for predicting UCP3 variation.

Discussion: The strong correlation of UCP expression and decrease in IMTG levels suggests that triglyceride content plays an even more important role in the regulation of UCP gene expression than the circulating levels of free fatty acids or the achieved degree of weight loss.