Evidence for a compensated thermogenic defect in transgenic mice lacking the mitochondrial glycerol-3-phosphate dehydrogenase gene.

A role for mitochondrial glycerol-3-phosphate dehydrogenase (mGPD) in thermogenesis was investigated in transgenic mice lacking the mGPD gene (mGPD−/−). Reared and studied at 22 C, these mice have a small, but significant, reduction (7–10%) in energy expenditure, as evidenced by oxygen consumption (QO2) and food intake, and show signs of increased brown adipose tissue (BAT) stimulation, higher plasma T4 and T3 concentrations, as well as increased uncoupling protein 3 (UCP3) expression in muscle. When acclimated at thermoneutrality temperature (32 C), QO2 decreased in both genotypes, but the difference between them widened to 16%, whereas BAT underwent atrophy, and plasma T4 and T3 levels and UCP3 mRNA decreased, yet T3 and UCP3 persisted at significantly higher levels in mGPD−/− mice. Such differences disappeared when the mice were rendered hypothyroid. A compensatory role for the observed changes in BAT, thyroid hormone levels, and UCP3 was investigated with a 2-h cold challenge of 12 C in euthyroid and ...