Journal Article

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

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

2019

Overview

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. Patients with aldolase B deficiency, a defect in fructose metabolism, are characterized by increased hepatic fat content and glucose intolerance compared with age-, sex-, and BMI-matched controls.

• Publisher: Endocrine Society,Copyright Oxford University Press,Oxford University Press
• Subject: 3-Hydroxybutyric Acid - blood / Adult / Blood Glucose - metabolism / Body Composition / Body Mass Index / Case-Control Studies / Clinics / Dextrose / Diet / Enzymes / Ethylenediaminetetraacetic acid / Fatty liver / Female / Fructose / Fructose Intolerance - diagnostic imaging / Fructose Intolerance - metabolism / Fructose-Bisphosphate Aldolase - deficiency / Genetics & genetic processes / Glucose / Glucose - metabolism / Génétique & processus génétiques / Humans / Inborn errors of metabolism / Intolerance / Lean body mass / Life sciences / Liver - diagnostic imaging / Liver - metabolism / Liver diseases / Magnetic Resonance Imaging / Magnetic resonance spectroscopy / Male / Metabolism / Metabolism, Inborn Errors - metabolism / Middle Aged / Nuclear magnetic resonance spectroscopy / Oxidation / Pathogenesis / Phosphates / Sciences du vivant / Transferrin - analysis / Transferrins / Triglycerides / Triglycerides - metabolism / Type 2 diabetes / Young Adult