title: Opposing effects of fructokinase C and A isoforms on fructose-induced metabolic syndrome in mice.
abstract: Fructose intake from added sugars correlates with the epidemic rise in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Fructose intake also causes features of metabolic syndrome in laboratory animals and humans. The first enzyme in fructose metabolism is fructokinase, which exists as two isoforms, A and C. Here we show that fructose-induced metabolic syndrome is prevented in mice lacking both isoforms but is exacerbated in mice lacking fructokinase A. Fructokinase C is expressed primarily in liver, intestine, and kidney and has high affinity for fructose, resulting in rapid metabolism and marked ATP depletion. In contrast, fructokinase A is widely distributed, has low affinity for fructose, and has less dramatic effects on ATP levels. By reducing the amount of fructose for metabolism in the liver, fructokinase A protects against fructokinase C-mediated metabolic syndrome. These studies provide insights into the mechanisms by which fructose causes obesity and metabolic syndrome.
authors.affiliation: Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Takuji
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa
authors.forename: Myphuong T
authors.initials: MT
authors.lastname: Le
authors.forename: Gabriela E
authors.initials: GE
authors.lastname: Garcia
authors.forename: Christine P
authors.initials: CP
authors.lastname: Diggle
authors.forename: Paul S
authors.initials: PS
authors.lastname: Maclean
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jackman
authors.forename: Aruna
authors.initials: A
authors.lastname: Asipu
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Roncal-Jimenez
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosugi
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rivard
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodriguez-Iturbe
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.forename: David T
authors.initials: DT
authors.lastname: Bonthron
authors.forename: Yuri Y
authors.initials: YY
authors.lastname: Sautin
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005631:Fructokinases / Q000378:metabolism*; D005632:Fructose / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D024821:Metabolic Syndrome / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D007527:Isoenzymes; D005632:Fructose; D005631:Fructokinases; C046173:fructokinase