Patients with aldolase B deficiency are characterized by increased intrahepatic triglyceride content
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 conver...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Oxford University Press
2019
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| _version_ | 1826304317894688768 |
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| author | Simons, N Debray, FG Schaper, NC Kooi, ME Feskens, EJM Hollak, CEM Lindeboom, L Koek, GH Bons, JAP Lefeber, DJ Hodson, L Schalkwijk, CG Stehouwer, CDA Cassiman, D Brouwers, MCGJ |
| author_facet | Simons, N Debray, FG Schaper, NC Kooi, ME Feskens, EJM Hollak, CEM Lindeboom, L Koek, GH Bons, JAP Lefeber, DJ Hodson, L Schalkwijk, CG Stehouwer, CDA Cassiman, D Brouwers, MCGJ |
| author_sort | Simons, N |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:16:00Z |
| format | Journal article |
| id | oxford-uuid:f119190f-a432-4281-a1e5-dd7991c4e5dc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:16:00Z |
| publishDate | 2019 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:f119190f-a432-4281-a1e5-dd7991c4e5dc2022-03-27T11:53:33ZPatients with aldolase B deficiency are characterized by increased intrahepatic triglyceride contentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f119190f-a432-4281-a1e5-dd7991c4e5dcEnglishSymplectic ElementsOxford University Press2019Simons, NDebray, FGSchaper, NCKooi, MEFeskens, EJMHollak, CEMLindeboom, LKoek, GHBons, JAPLefeber, DJHodson, LSchalkwijk, CGStehouwer, CDACassiman, DBrouwers, MCGJCONTEXT: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. |
| spellingShingle | Simons, N Debray, FG Schaper, NC Kooi, ME Feskens, EJM Hollak, CEM Lindeboom, L Koek, GH Bons, JAP Lefeber, DJ Hodson, L Schalkwijk, CG Stehouwer, CDA Cassiman, D Brouwers, MCGJ Patients with aldolase B deficiency are characterized by increased intrahepatic triglyceride content |
| title | Patients with aldolase B deficiency are characterized by increased intrahepatic triglyceride content |
| title_full | Patients with aldolase B deficiency are characterized by increased intrahepatic triglyceride content |
| title_fullStr | Patients with aldolase B deficiency are characterized by increased intrahepatic triglyceride content |
| title_full_unstemmed | Patients with aldolase B deficiency are characterized by increased intrahepatic triglyceride content |
| title_short | Patients with aldolase B deficiency are characterized by increased intrahepatic triglyceride content |
| title_sort | patients with aldolase b deficiency are characterized by increased intrahepatic triglyceride content |
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