TY - JOUR
T1 - Recent advances in the pathogenesis of hereditary fructose intolerance
T2 - implications for its treatment and the understanding of fructose-induced non-alcoholic fatty liver disease
AU - Buziau, Amee M.
AU - Schalkwijk, Casper G.
AU - Stehouwer, Coen D. A.
AU - Tolan, Dean R.
AU - Brouwers, Martijn C. G. J.
N1 - Funding Information:
The study in HFI patients was subsidized by the Netherlands Heart Foundation (#2015T042) and Stofwisselkracht. MB received a personal grant from the Diabetes Foundation (#2017.82.004). DT was supported by Colorado Research Partners LLC and National Institutes of Health (R01DK108859).
Funding Information:
The study in HFI patients was subsidized by the Netherlands Heart Foundation (#2015T042) and Stofwisselkracht. MB received a personal grant from the Diabetes Foundation (#2017.82.004). DT was supported by Colorado Research Partners LLC and National Institutes of Health (R01DK108859).
Publisher Copyright:
© 2019, Springer Nature Switzerland AG.
PY - 2020/5
Y1 - 2020/5
N2 - Hereditary fructose intolerance (HFI) is a rare inborn disease characterized by a deficiency in aldolase B, which catalyzes the cleavage of fructose 1,6-bisphosphate and fructose 1-phosphate (Fru 1P) to triose molecules. In patients with HFI, ingestion of fructose results in accumulation of Fru 1P and depletion of ATP, which are believed to cause symptoms, such as nausea, vomiting, hypoglycemia, and liver and kidney failure. These sequelae can be prevented by a fructose-restricted diet. Recent studies in aldolase B-deficient mice and HFI patients have provided more insight into the pathogenesis of HFI, in particular the liver phenotype. Both aldolase B-deficient mice (fed a very low fructose diet) and HFI patients (treated with a fructose-restricted diet) displayed greater intrahepatic fat content when compared to controls. The liver phenotype in aldolase B-deficient mice was prevented by reduction in intrahepatic Fru 1P concentrations by crossing these mice with mice deficient for ketohexokinase, the enzyme that catalyzes the synthesis of Fru 1P. These new findings not only provide a potential novel treatment for HFI, but lend insight into the pathogenesis of fructose-induced non-alcoholic fatty liver disease (NAFLD), which has raised to epidemic proportions in Western society. This narrative review summarizes the most recent advances in the pathogenesis of HFI and discusses the implications for the understanding and treatment of fructose-induced NAFLD.
AB - Hereditary fructose intolerance (HFI) is a rare inborn disease characterized by a deficiency in aldolase B, which catalyzes the cleavage of fructose 1,6-bisphosphate and fructose 1-phosphate (Fru 1P) to triose molecules. In patients with HFI, ingestion of fructose results in accumulation of Fru 1P and depletion of ATP, which are believed to cause symptoms, such as nausea, vomiting, hypoglycemia, and liver and kidney failure. These sequelae can be prevented by a fructose-restricted diet. Recent studies in aldolase B-deficient mice and HFI patients have provided more insight into the pathogenesis of HFI, in particular the liver phenotype. Both aldolase B-deficient mice (fed a very low fructose diet) and HFI patients (treated with a fructose-restricted diet) displayed greater intrahepatic fat content when compared to controls. The liver phenotype in aldolase B-deficient mice was prevented by reduction in intrahepatic Fru 1P concentrations by crossing these mice with mice deficient for ketohexokinase, the enzyme that catalyzes the synthesis of Fru 1P. These new findings not only provide a potential novel treatment for HFI, but lend insight into the pathogenesis of fructose-induced non-alcoholic fatty liver disease (NAFLD), which has raised to epidemic proportions in Western society. This narrative review summarizes the most recent advances in the pathogenesis of HFI and discusses the implications for the understanding and treatment of fructose-induced NAFLD.
KW - Hereditary fructose intolerance
KW - Glucokinase regulatory protein
KW - Ketohexokinase
KW - Fructose
KW - De novo lipogenesis
KW - Non-alcoholic fatty liver disease
KW - HUMAN ALDOLASE-B
KW - REGULATORY PROTEIN
KW - URIC-ACID
KW - PLASMA TRIGLYCERIDE
KW - HEPATIC LIPOGENESIS
KW - MOLECULAR ANALYSIS
KW - METABOLIC SYNDROME
KW - FASTING GLUCOSE
KW - GLUCOKINASE
KW - VARIANT
U2 - 10.1007/s00018-019-03348-2
DO - 10.1007/s00018-019-03348-2
M3 - (Systematic) Review article
C2 - 31713637
SN - 1420-682X
VL - 77
SP - 1709
EP - 1719
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
IS - 9
ER -