Mice with deletion of the mitochondrial glycerol-3-phosphate dehydrogenase gene exhibit a thrifty phenotype: effect of gender

To define the role of mitochondrial glycerol-3-phosphate dehydrogenase (mGPD; EC 1.1.99.5) in energy balance and intermediary metabolism, we studied transgenic mice not expressing mGPD (mGPD−/−). These mice had ≈14% lower blood glucose; ≈50% higher serum glycerol; ≈80% higher serum triglycerides; and at thermoneutrality, their energy expenditure (Qo2) was 15% lower than in wild-type (WT) mice. Glycerol-3-phosphate levels and lactate-to-pyruvate ratios were threefold elevated in muscle, but not in liver, of mGPD−/− mice. WT and mGPD−/− mice were then challenged with a high-fat diet, fasting, or food restriction. The high-fat diet caused more weight gain and adiposity in mGPD−/− than in WT female mice, without the genotype differentially affecting Qo2 or energy intake. After a 30-h fast, WT female lost 60% more weight than mGPD−/− mice but these latter became more hypothermic. When energy intake was restricted to 50–70% of the ad libitum intake for 10 days, mGPD−/− female mice lost less weight than WT contr...