Reduced Expression of Uncoupling Protein 2 in Adipose Tissue in Patients with Hypothyroidism

CONTEXT: Thyroid disease is associated with major metabolic changes, comprising changes in lipid metabolism. Thyroid hormones have previously been shown to increase UCP2 mRNA expression in fat biopsies from hyperthyroid patients, but data from hypothyroid patients have so far not been reported.

PATIENTS AND METHODS: Eleven hypothyroid patients were studied before and after l-T(4) replacement, and 10 healthy controls matched for sex, age, and body mass index were studied once. Subcutaneous fat biopsies were performed, and UCP2 mRNA expression was measured in these biopsies. Patients also underwent indirect calorimetry and blood sampling.

RESULTS: Patients were profoundly hypothyroid at study entry with significantly increased TSH levels (149.9 + or - 60.4 mU/liter). UCP2 mRNA expression was reduced in the hypothyroid state as compared with the euthyroid state (0.0081 + or - 0.0028 vs. 0.0420 + or - 0.0076, P < 0.01). Using pooled data from hypothyroid patients and control subjects, we found positive correlations between lipid oxidation rates and adipose tissue UCP2 expression (r = 0.63; P < 0.004), basal free fatty acid levels and UCP2 expression (r = 0.51; P < 0.03), and T(3) levels and UCP2 (r = 0.69; P < 0.001).

CONCLUSION: Our study demonstrates that hypothyroidism is associated with a profound decrease in UCP2 mRNA expression. It supports the notion that UCP2 is a determinant of fat oxidation pathways and may be involved in the changes seen in the metabolic pathways in thyroid disease.