title: Glycerol-3-phosphate dehydrogenase 1 deficiency induces compensatory amino acid metabolism during fasting in mice.
abstract: BACKGROUND
  Glucose is used as an energy source in many organs and obtained from dietary carbohydrates. However, when the external energy supply is interrupted, e.g., during fasting, carbohydrates preserved in the liver and glycogenic precursors derived from other organs are used to maintain blood glucose levels. Glycerol and glycogenic amino acids derived from adipocytes and skeletal muscles are utilized as glycogenic precursors. Glycerol-3-phosphate dehydrogenase 1 (GPD1), an NAD+/NADH-dependent enzyme present in the cytosol, catalyzes the reversible conversion of glycerol-3-phosphate (G3P) to dihydroxyacetone phosphate (DHAP). Since G3P is one of the substrates utilized for gluconeogenesis in the liver, the conversion of G3P to DHAP by GPD1 is essential for maintaining blood glucose levels during fasting. We focused on GPD1 and examined its roles in gluconeogenesis during fasting.
  
  
  METHODS
  Using GPD1 null model BALB/cHeA mice (HeA mice), we measured gluconeogenesis from glycerol and the change of blood glucose levels under fasting conditions. We also measured gene expression related to gluconeogenesis in the liver and protein metabolism in skeletal muscle. BALB/cBy mice (By mice) were used as a control.
  
  
  RESULTS
  The blood glucose levels in the HeA mice were lower than that in the By mice after glycerol administration. Although lack of GPD1 inhibited gluconeogenesis from glycerol, blood glucose levels in the HeA mice after 1-4h of fasting were significantly higher than that in the By mice. Muscle protein synthesis in HeA mice was significantly lower than that in the By mice. Moreover, blood alanine levels and usage of alanine for gluconeogenesis in the liver were significantly higher in the HeA mice than that in the By mice.
  
  
  CONCLUSIONS
  Although these data indicate that a lack of GPD1 inhibits gluconeogenesis from glycerol, chronic GPD1 deficiency may induce an adaptation that enhances gluconeogenesis from glycogenic amino acids.
authors.affiliation: Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: s15603@u-shizuoka-ken.ac.jp.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: moritaa@u-shizuoka-ken.ac.jp.
authors.forename: Akihito
authors.initials: A
authors.lastname: Morita
authors.affiliation: Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai 599-8570, Japan. Electronic address: morin@b.s.osakafu-u.ac.jp.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Mori
authors.affiliation: Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. Electronic address: miura@u-shizuoka-ken.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miura
mesh_terms: D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004098:Dihydroxyacetone / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D005943:Gluconeogenesis / Q000235:genetics; D005990:Glycerol / Q000378:metabolism; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+) / Q000172:deficiency* / Q000235:genetics; D005994:Glycerophosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D005994:Glycerophosphates; D009124:Muscle Proteins; D006003:Glycogen; C029620:alpha-glycerophosphoric acid; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D004098:Dihydroxyacetone; D000409:Alanine; D005990:Glycerol
keywords: BALB/cHeA; Gluconeogenesis; Glycerol; Glycogenic amino acid