title: Hepatic De Novo Lipogenesis in Obese Youth Is Modulated by a Common Variant in the GCKR Gene.
abstract: OBJECTIVE
  This study's aim was to evaluate whether the GCKR rs1260326 variant increases hepatic de novo lipogenesis (DNL).
  
  
  METHODS
  To test this hypothesis, 14 adolescents, seven homozygous for the common allele (CC) and seven homozygous for the risk allele (TT), underwent measurement of hepatic DNL during the fasting state and after consumption of a carbohydrate (CHO) drink (75 g glucose and 25 g fructose). DNL was assessed through incorporation of deuterium in the palmitate contained in the very low-density lipoprotein.
  
  
  RESULTS
  Subjects with TT demonstrated higher fasting fractional DNL (P = .036) and a lower increase in fractional DNL after the CHO challenge (P = .016). With regard to absolute lipogenesis, TT subjects had both higher fasting rates (P = .015) and 44% greater area under the curve of absolute lipogenesis during the study (P = .016), compared to CC subjects. Furthermore, subjects carrying the TT genotype showed higher basal rates of glucose oxidation (P = .0028) and a lower ability than CC subjects to increase the rates of glucose oxidation after the CHO load (P = .054).
  
  
  CONCLUSIONS
  This study reports for the first time rates of DNL in obese adolescents and suggests that the GCKR rs1260326 gene variant, which is associated with greater glycolysis, increases hepatic DNL. These data highlight the role of glycolytic carbon flux in liver lipid synthesis and hypertriglyceridemia in these youngsters.
authors.affiliation: Department of Pediatrics (N.S., S.C., B.P., M.V.N., M.S.), Yale University School of Medicine, New Haven, Connecticut 06520; and Department of Medicine (E.J.P.), University of Missouri, Colombia, Missouri 65211.
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.affiliation: Department of Pediatrics (N.S., S.C., B.P., M.V.N., M.S.), Yale University School of Medicine, New Haven, Connecticut 06520; and Department of Medicine (E.J.P.), University of Missouri, Colombia, Missouri 65211.
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
authors.affiliation: Department of Pediatrics (N.S., S.C., B.P., M.V.N., M.S.), Yale University School of Medicine, New Haven, Connecticut 06520; and Department of Medicine (E.J.P.), University of Missouri, Colombia, Missouri 65211.
authors.forename: Bridget
authors.initials: B
authors.lastname: Pierpont
authors.affiliation: Department of Pediatrics (N.S., S.C., B.P., M.V.N., M.S.), Yale University School of Medicine, New Haven, Connecticut 06520; and Department of Medicine (E.J.P.), University of Missouri, Colombia, Missouri 65211.
authors.forename: Michelle
authors.initials: M
authors.lastname: Van Name
authors.affiliation: Department of Pediatrics (N.S., S.C., B.P., M.V.N., M.S.), Yale University School of Medicine, New Haven, Connecticut 06520; and Department of Medicine (E.J.P.), University of Missouri, Colombia, Missouri 65211.
authors.forename: Mary
authors.initials: M
authors.lastname: Savoye
authors.affiliation: Department of Pediatrics (N.S., S.C., B.P., M.V.N., M.S.), Yale University School of Medicine, New Haven, Connecticut 06520; and Department of Medicine (E.J.P.), University of Missouri, Colombia, Missouri 65211.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Parks
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D002153:Calorimetry, Indirect; D015331:Cohort Studies; D005234:Fatty Liver / Q000150:complications / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D050155:Lipogenesis / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D063766:Pediatric Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485100:GCKR protein, human