Metabolic consequences of deleting the mitochondrial glycerol-3-phosphate dehydrogenase gene in mice

To define the role of mitochondrial glycerol-3-phosphate dehydrogenase (EC 1.1.99.5; mGPD) in energy balance and intermediary metabolism, we studied female transgenic mice lacking the mGPD gene (mGPD-/-). These mice had higher serum glycerol and triglycerides; lower body weight, blood glucose, and energy expenditure (QO2); and higher glycerol-3-phosphate and lactate/pyruvate ratio in muscle than controls with wild type genotype (WT). When given a high fat/low carbohydrate diet, mGPD-/- mice gain more weight than WT, without the genotype differentially affecting QO2 or calorie intake. On a low fat/high carbohydrate diet, mGPD-/- mice failed to increase QO2 as the WT and gained more weight. After a 30-hour fasting or food restriction to 70% for 10 days, WT lost significantly more weight than mGPD-/- mice, but these latter had lower body temperature and QO2. Thus, mGPD-/- mice exhibit a thrifty phenotype largely resulting from reduced obligatory thermogenesis.