Patients with aldolase B deficiency are characterized by an increased intrahepatic triglyceride content

N. Simons, F.G. Debray, N.C. Schaper, M.E. Kooi, E.J.M. Feskens, C.E.M. Hollak, L. Lindeboom, G.H. Koek, J.A.P. Bons, D.J. Lefeber, L. Hodson, Casper G. Schalkwijk, Coen D.A. Stehouwer, D. Cassiman, M.C.G.J. Brouwers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

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/m2, 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 β-hydroxybutyrate, a biomarker of hepatic β-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 β-oxidation are involved in the pathogenesis.
Original languageEnglish
Pages (from-to)5056-5064
JournalJournal of Clinical Endocrinology and Metabolism
Volume104
Issue number11
DOIs
Publication statusPublished - Nov 2019

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