Aldolase-B knockout in mice phenocopies hereditary fructose intolerance in humans

Oppelt, Sarah A.; Sennott, Erin M.; Tolan, Dean R.

doi:10.1016/j.ymgme.2015.01.001

Cited by 44 publications

(37 citation statements)

References 36 publications

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“…Previously, our group demonstrated that mice lacking aldolase B are phenotypically identical to individuals with HFI and that after exposure to fructose they are characterized by a high incidence of lethality, inflammation, fatty liver, and growth retardation (19). Since Khk is located upstream to aldolase B in the metabolism of fructose, and Khk is necessary for fructose-dependent ATP depletion and the generation of Fru1-P, the hypothesis that blockade of Khk activity would offer protection from the sequela of HFI was tested.…”

Section: Resultsmentioning

confidence: 99%

“…AldoB-KO and Khk-KO mice in the C57BL/6 background were generated as previously described (19,24,57). Mice were maintained in temperature-and humidity-controlled specific pathogen-free conditions on a 14-hour-dark, 10-hour-light cycle, and allowed ad libitum access to normal laboratory chow (Harlan Teklad, catalog 2920X) (Figure 3 and Figure 5) or a fructose-free diet (Bioserv, catalog F6700) for AldoB-KO mice.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, an aldolase B knockout (AldoB-KO) mouse was shown to have symptoms similar to HFI (19). In the present report, the hypothesis that blocking Khk activity will prevent HFI in mice was tested using Khk-KO mice.…”

Section: Introductionmentioning

confidence: 94%

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Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice

Lanaspa¹,

Andrés-Hernando²,

Orlicky³

et al. 2018

Journal of Clinical Investigation

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice

Lanaspa¹,

Andrés-Hernando²,

Orlicky³

et al. 2018

Journal of Clinical Investigation

Self Cite

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“…The precise mechanisms by which ALDOB deficiency causes symptoms are not entirely clear. An Aldob-deficient mouse model mimics the human HFI condition (98). These mice fail to thrive and die when exposed to highfructose diets.…”

Section: Genetic Lessons About Fructose Metabolismmentioning

confidence: 99%

“…These mice fail to thrive and die when exposed to highfructose diets. Interestingly, even on a fructose-free diet, Aldobdeficient mice develop steatosis (98), possibly due to impaired metabolism of endogenously synthesized fructose (99).…”

Section: Genetic Lessons About Fructose Metabolismmentioning

confidence: 99%

Fructose metabolism and metabolic disease

Hannou

Haslam

McKeown

et al. 2018

Journal of Clinical Investigation

417

356

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Fructose Metabolism Disorders

Cox

2015

Encyclopedia of Life Sciences

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Fructose occurs in fruit, nuts, honey and some vegetables as well as a component of the disaccharide, sucrose; it is not present in human or cows' milk. Since the emergence of trade in cane‐ and beet‐sugar, fructose is now a near‐ubiquitous component of the modern diet; and consumption has continued to increase across the developed world. Industrial generation of high‐fructose products from starch in maize (corn) and other agricultural crops now enhances the availability of the fructose in commercial foods and comestibles – especially the so‐called ‘health’ or ‘energy’ drinks. High consumption of fructose and related sugars is implicated in the so‐called ‘Metabolic Syndrome’ associated with obesity, type 2 diabetes mellitus, hyperlipidaemia and premature cardiovascular disease. After incorporation into the body from the diet, entry of fructose into cells occurs rapidly but also independently of regulatory influences of insulin: as fructose esters participate critically in intermediary metabolism, inherited defects of enzymes involved in handling of exogenous fructose may have profound pathological effects. Examples are essential fructosuria, hereditary fructose intolerance and fructose‐1,6‐bisphosphatase deficiency. Key Concepts Fructose occurs as a free monosaccharide or as a component of sucrose; it is also derived from the sugar alcohol, sorbitol. Uptake of free fructose into cells via the GLUT 5 transporter occurs rapidly and is independent of insulin. Rare inborn errors of fructose metabolism affect this specialised pathway for metabolic incorporation in the liver, kidney and small intestine. With the appropriate level of diagnostic suspicion, facile detection of the most life threatening of these diseases is now possible by molecular analysis of genomic DNA, thus avoiding invasive biochemical investigations. Global manufacture of sugar as a commodity started with the European and Arabic exploration of Africa and use of slave labour in colonial sugar plantations. Changing dietary habits and global trends in food manufacture with intensified industrialisation of sugar production have exposed the toxic effects of fructose. Excessive ingestion of fructose and its congeners is injurious: the sugar influences the energy status of cells and stimulates hepatic lipogenesis; these effects are exaggerated in patients with defective intermediary metabolism of fructose.

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Aldolase-B knockout in mice phenocopies hereditary fructose intolerance in humans

Cited by 44 publications

References 36 publications

Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice

Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice

Fructose metabolism and metabolic disease

Fructose Metabolism Disorders

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