title: Normal thyroid thermogenesis but reduced viability and adiposity in mice lacking the mitochondrial glycerol phosphate dehydrogenase.
abstract: The mitochondrial glycerol phosphate dehydrogenase (mGPD) is important for metabolism of glycerol phosphate for gluconeogenesis or energy production and has been implicated in thermogenesis induced by cold and thyroid hormone treatment. mGPD in combination with the cytosolic glycerol phosphate dehydrogenase (cGPD) is proposed to form the glycerol phosphate shuttle, catalyzing the interconversion of dihydroxyacetone phosphate and glycerol phosphate with net oxidation of cytosolic NADH. We made a targeted deletion in Gdm1 and produced mice lacking mGPD. On a C57BL/6J background these mice showed a 50% reduction in viability compared with wild-type littermates. Uncoupling protein-1 mRNA levels in brown adipose tissue did not differ between mGPD knockout and control pups, suggesting normal thermogenesis. Pups lacking mGPD had decreased liver ATP and slightly increased liver glycerol phosphate. In contrast, liver and muscle metabolites were normal in adult animals. Adult mGPD knockout animals had a normal cold tolerance, normal circadian rhythm in body temperature, and demonstrated a normal temperature increase in response to thyroid hormone. However, they were found to have a lower body mass index, a 40% reduction in the weight of white adipose tissue, and a slightly lower fasting blood glucose than controls. The phenotype may be secondary to consequences of the obligatory production of cytosolic NADH from glycerol metabolism in the mGPD knockout animal. We conclude that, although mGPD is not essential for thyroid thermogenesis, variations in its function affect viability and adiposity in mice.
authors.affiliation: Department of Pediatrics, University of Wisconsin, Madison, Wisconsin 53706, USA. ljbrown2@facstaff.wisc.edu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Brown
authors.forename: Robert A
authors.initials: RA
authors.lastname: Koza
authors.forename: Carrie
authors.initials: C
authors.lastname: Everett
authors.forename: Marc L
authors.initials: ML
authors.lastname: Reitman
authors.forename: Linda
authors.initials: L
authors.lastname: Marshall
authors.forename: Leonard A
authors.initials: LA
authors.lastname: Fahien
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Kozak
authors.forename: Michael J
authors.initials: MJ
authors.lastname: MacDonald
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000254:growth & development*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D003600:Cytosol / Q000201:enzymology; D005260:Female; D005822:Genetic Vectors; D005838:Genotype; D005990:Glycerol / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology*; D008954:Models, Biological; D008957:Models, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D016019:Survival Analysis; D013696:Temperature; D022722:Thermogenesis; D013961:Thyroid Gland / Q000502:physiology*; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D005993:Glycerolphosphate Dehydrogenase; D005990:Glycerol