TY - JOUR
T1 - Patients With Aldolase B Deficiency Are Characterized by Increased Intrahepatic Triglyceride Content
AU - Simons, Nynke
AU - Debray, Francois-Guillaume
AU - Schaper, Nicolaas C.
AU - Kooi, M. Eline
AU - Feskens, Edith J. M.
AU - Hollak, Carla E. M.
AU - Lindeboom, Lucas
AU - Koek, Ger H.
AU - Bons, Judith A. P.
AU - Lefeber, Dirk J.
AU - Hodson, Leanne
AU - Schalkwijk, Casper G.
AU - Stehouwer, Coen D. A.
AU - Cassiman, David
AU - Brouwers, Martijn C. G. J.
N1 - Publisher Copyright:
Copyright © 2019 Endocrine Society.
PY - 2019/11
Y1 - 2019/11
N2 - Context: There is an ongoing debate about whether and how fructose is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A recent experimental study showed an increased intrahepatic triglyceride (IHTG) content in mice deficient for aldolase B (aldo B-/-), the enzyme that converts fructose-1-phosphate to triose phosphates.Objective: To translate these experimental findings to the human situation.Design: Case-control study.Setting: Outpatient clinic for inborn errors of metabolism.Patients or Other Participants: Patients with hereditary fructose intolerance, a rare inborn error of metabolism caused by a defect in aldolase B (n = 15), and healthy persons matched for age, sex, and body mass index (BMI) (n =15).Main Outcome Measure: IHTG content, assessed by proton magnetic resonance spectroscopy.Results: IHTG content was higher in aldo B-/- patients than controls (2.5% vs 0.6%; P = 0.001) on a background of lean body mass (median BMI, 20.4 and 21.8 kg/m(2), respectively). Glucose excursions during an oral glucose load were higher in aldo B-/- patients (P = 0.043). Hypoglycosylated transferrin, a surrogate marker for hepatic fructose-1-phosphate concentrations, was more abundant in aldo B-/- patients than in controls (P <0.001). Finally, plasma beta-hydroxybutyrate, a biomarker of hepatic beta-oxidation, was lower in aldo B-/- patients than controls (P = 0.009).Conclusions: This study extends previous experimental findings by demonstrating that aldolase B deficiency also results in IHTG accumulation in humans. It suggests that the accumulation of fructose-1-phosphate and impairment of beta-oxidation are involved in the pathogenesis.
AB - Context: There is an ongoing debate about whether and how fructose is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). A recent experimental study showed an increased intrahepatic triglyceride (IHTG) content in mice deficient for aldolase B (aldo B-/-), the enzyme that converts fructose-1-phosphate to triose phosphates.Objective: To translate these experimental findings to the human situation.Design: Case-control study.Setting: Outpatient clinic for inborn errors of metabolism.Patients or Other Participants: Patients with hereditary fructose intolerance, a rare inborn error of metabolism caused by a defect in aldolase B (n = 15), and healthy persons matched for age, sex, and body mass index (BMI) (n =15).Main Outcome Measure: IHTG content, assessed by proton magnetic resonance spectroscopy.Results: IHTG content was higher in aldo B-/- patients than controls (2.5% vs 0.6%; P = 0.001) on a background of lean body mass (median BMI, 20.4 and 21.8 kg/m(2), respectively). Glucose excursions during an oral glucose load were higher in aldo B-/- patients (P = 0.043). Hypoglycosylated transferrin, a surrogate marker for hepatic fructose-1-phosphate concentrations, was more abundant in aldo B-/- patients than in controls (P <0.001). Finally, plasma beta-hydroxybutyrate, a biomarker of hepatic beta-oxidation, was lower in aldo B-/- patients than controls (P = 0.009).Conclusions: This study extends previous experimental findings by demonstrating that aldolase B deficiency also results in IHTG accumulation in humans. It suggests that the accumulation of fructose-1-phosphate and impairment of beta-oxidation are involved in the pathogenesis.
KW - FATTY LIVER-DISEASE
KW - HEREDITARY FRUCTOSE INTOLERANCE
KW - MAGNETIC-RESONANCE-SPECTROSCOPY
KW - INSULIN SENSITIVITY
KW - HEPATIC STEATOSIS
KW - DIETS
KW - ACIDS
KW - GLYCOSYLATION
KW - CONSUMPTION
KW - PREVALENCE
U2 - 10.1210/jc.2018-02795
DO - 10.1210/jc.2018-02795
M3 - Article
C2 - 30901028
SN - 0021-972X
VL - 104
SP - 5056
EP - 5064
JO - Journal of Clinical Endocrinology & Metabolism
JF - Journal of Clinical Endocrinology & Metabolism
IS - 11
ER -