Patients With Aldolase B Deficiency Are Characterized by Increased Intrahepatic Triglyceride Content

Nynke Simons, François-Guillaume Debray, Nicolaas C Schaper, M Eline Kooi, Edith J M Feskens, Carla E M Hollak, Lucas Lindeboom, Ger H Koek, Judith A P Bons, Dirk J Lefeber, Leanne Hodson, Casper G Schalkwijk, Coen D A Stehouwer, David Cassiman, Martijn C G J Brouwers

Research output: Contribution to journalArticleAcademicpeer-review

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
Number of pages9
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number11
DOIs
Publication statusPublished - 22 Mar 2019
Externally publishedYes

Keywords

  • 3-hydroxybutyric acid/blood
  • adult
  • blood glucose/metabolism
  • body composition
  • body mass index
  • case-control studies
  • diet
  • female
  • fructose intolerance/diagnostic imaging
  • fructose-bisphosphate aldolase/deficiency
  • glucose/metabolism
  • humans
  • liver/diagnostic imaging
  • magnetic resonance imaging
  • male
  • metabolism, inborn errors/metabolism
  • middle aged
  • transferrin/analysis
  • triglycerides/metabolism
  • young adult

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