title: Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome.
abstract: Carbohydrates with high glycaemic index are proposed to promote the development of obesity, insulin resistance and fatty liver, but the mechanism by which this occurs remains unknown. High serum glucose concentrations are known to induce the polyol pathway and increase fructose generation in the liver. Here we show that this hepatic, endogenously produced fructose causes systemic metabolic changes. We demonstrate that mice unable to metabolize fructose are protected from an increase in energy intake and body weight, visceral obesity, fatty liver, elevated insulin levels and hyperleptinaemia after exposure to 10% glucose for 14 weeks. In normal mice, glucose consumption is accompanied by aldose reductase and polyol pathway activation in steatotic areas. In this regard, we show that aldose reductase-deficient mice are protected against glucose-induced fatty liver. We conclude that endogenous fructose generation and metabolism in the liver represents an important mechanism by which glucose promotes the development of metabolic syndrome.
authors.affiliation: 1] Division of Renal Diseases and Hypertension, University of Colorado, 12700 East 19th Avenue, Room 7015, Denver, Colorado 80045, USA [2].
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Lanaspa
authors.forename: Takuji
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Nanxing
authors.initials: N
authors.lastname: Li
authors.forename: Christina
authors.initials: C
authors.lastname: Cicerchi
authors.forename: David J
authors.initials: DJ
authors.lastname: Orlicky
authors.forename: Philip
authors.initials: P
authors.lastname: Ruzycki
authors.forename: Philip
authors.initials: P
authors.lastname: Ruzicky
authors.forename: Christopher
authors.initials: C
authors.lastname: Rivard
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Inaba
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Roncal-Jimenez
authors.forename: Elise S
authors.initials: ES
authors.lastname: Bales
authors.forename: Christine P
authors.initials: CP
authors.lastname: Diggle
authors.forename: Aruna
authors.initials: A
authors.lastname: Asipu
authors.forename: J Mark
authors.initials: JM
authors.lastname: Petrash
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosugi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Laura G
authors.initials: LG
authors.lastname: Sanchez-Lozada
authors.forename: James L
authors.initials: JL
authors.lastname: McManaman
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: D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D005234:Fatty Liver / Q000378:metabolism; D005247:Feeding Behavior; D005631:Fructokinases / Q000172:deficiency / Q000378:metabolism; D005632:Fructose / Q000096:biosynthesis* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011108:Polymers / Q000378:metabolism
chemical_list: D011108:Polymers; C024617:polyol; D005632:Fructose; D000449:Aldehyde Reductase; D005631:Fructokinases; C046173:fructokinase; D005947:Glucose
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