Lipidomics uncovers metabolic manifestations related to liver steatosis and low-grade systemic inflammation in diet-treated hereditary fructose intolerance patients
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND AIMS: Hereditary Fructose Intolerance (HFI), a rare autosomal recessive metabolic disorder, has historically been considered benign when treated with a lifelong fructose-, sucrose and sorbitol-restricted diet. However, adverse metabolic manifestations have recently been reported in treated HFI patients. As serum metabolomics offers a valuable tool for assessing metabolic manifestations underlying inherited metabolic disorders, we aim to compare the serum lipidomic profile of HFI-treated patients with age-, gender-, and body mass index-matched healthy controls. METHODS: H NMR) spectroscopy test, sialotransferrin analysis, and serum multiplex analysis of cytokines/chemokines were performed. RESULTS: The HFI patients exhibited a distinct serum lipidomic profile showing separate clusters in the multivariate analysis between these patients and the healthy controls. Top-interacting network analysis revealed abnormalities in lipid metabolism and inflammation as hallmarks of HFI. Indeed, significant liver steatosis, assessed by MRS proton density fat fraction (MRS-PDFF), was present in 75 % of HFI patients compared to 7 % in the control group. Moreover, low-grade systemic inflammation was highly prevalent in HFI patients, exhibiting elevated serum cytokines, C-reactive protein, acute phase proteins such as fibrinogen and ferritin, and increased low-grade inflammation score. Additionally, circulating glycoprotein acetyls (GlycA), a novel serum marker for low-grade inflammation, was significantly elevated in the HFI patients and associated with their lipidomic profile and markers of altered intestinal permeability, such as serum lipopolysaccharide binding protein. Furthermore, increased GlycA concentration in the HFI patients was associated with elevation of blood pressure and an altered serum lipoprotein profile, early factors of cardiovascular risk. CONCLUSIONS: Serum lipidomic study revealed previously unknown metabolic complications of HFI-treated patients. Notably, we have found that low-grade systemic inflammation is highly prevalent in the cohort of HFI patients and correlates with early factors of cardiovascular risk. Expanding our current understanding of the metabolic consequences in HFI-treated patients will provide the best care for patients.
Source: Clinical Nutrition
Authors: Javier de las Heras, María Unceta Suarez, Maria Mercado-Gómez, Leire Uraga Gracianteparaluceta, Xavier Buqué, Cristina Alonso, Marina Serrano-Macia, Carlos Alcalde, Ainara Cano, Irene González-Recio, Naroa Goikoetxea-Usandizaga, Edorta Mora, Amaya Belanger-Quintana, Elvira Cañedo-Villarroya, Leticia Ceberio, Silvia Chumillas-Calzada, Patricia Correcher, Dolores García-Arenas, Igor Gómez, Tomás Hernández, Elsa Izquierdo-García, Dámaris Martínez Chicano, Montserrat Morales, Consuelo Pedrón-Giner, Estrella Petrina Jáuregui, Luis Peña-Quintana, Paula Sánchez-Pintos, Juliana Serrano-Nieto, Irene Serrano-Gonzalo, Isidro Vitoria Miñana, J.A. Larena, María Luz Couce, María Luz Martínez-Chantar, Patricia Aspichueta, Teresa C. Delgado
Institutions: University of the Basque Country, Hospital de Cruces, CIC bioGUNE, OWL (Spain), Hospital Universitario Río Hortega, AZTI, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Hospital Universitario Ramón y Cajal, Hospital Infantil Universitario Niño Jesús, Hospital Universitario 12 De Octubre, Centre for Biomedical Network Research on Rare Diseases, Hospital Universitari i Politècnic La Fe, Hospital Sant Joan de Déu Barcelona, Hospital Universitario Araba, Hospital Universitario Infanta Leonor, Clinica Universidad de Navarra, Universidad de Las Palmas de Gran Canaria, Instituto de Investigación Sanitaria de Santiago, Hospital Regional Universitario de Málaga, Instituto de Investigación Sanitaria Aragón, Hospital de Galdakao, Ikerbasque
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,320
OpenAlex ID: W7131670320