High expression of thyroid hormone receptors and mitochondrial glycerol-3-phosphate dehydrogenase in the liver is linked to enhanced fatty acid oxidation in Lou/C rat strain resistant to obesity

Besides its well recognized role in lipid and carbohydratemetabolisms, glycerol is involved in the regulation of cellularenergy homeostasis via glycerol-3-phosphate, a key metabolitein the translocation of reducing power across the mitochondrialinner membrane with mitochondrial glycerol-3-phosphate dehydrogenase.Here, we report a high rate of gluconeogenesisfrom glycerol and fatty acid oxidation in hepatocytes fromLou/C, a peculiar rat strain derived from Wistar, which is resistantto age- and diet-related obesity. This feature, associatedwith elevated cellular respiration and cytosolic ATP/ADP andNAD/NADH ratios, was linked to a high expression and activityof mitochondrial glycerol-3-phosphate dehydrogenase.Interestingly, this strain exhibited high expression and proteincontent of thyroid hormone receptor, whereas circulating thyroidhormone levels were slightly decreased and hepatic thyroidhormone carrier MCT-8 mRNA levels were not modified. Wepropose that an enhanced liver thyroid hormone receptor inLou/C may explain its unique resistance to obesity by increasingfatty acid oxidation and lowering liver oxidative phosphorylationstoichiometry at the translocation of reducing power intomitochondria.