Impaired Metabolic Flexibility in the Osteoarthritis Process: A Study on Transmitochondrial Cybrids

Cells

Andrea Dalmao-Fernández¹  Ignacio Rego-Pérez¹  Mercedes Fernández-Moreno¹  MaríaE Vazquez-Mosquera¹  FranciscoJ. Blanco¹  Tamara Hermida-Gómez¹  Jenny Lund² 

[1] Grupo de Investigación en Reumatología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Agrupación estratégica CICA-INIBIC, Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas. Universidade da Coruña (UDC), 15006 A Coruña, Spain;Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, 0363 Oslo, Norway;

关键词: osteoarthritis;    transmitochondrial cybrids;    energy metabolism;    metabolic flexibility;   

DOI  :  10.3390/cells9040809

来源: DOAJ

【 摘 要 】

Osteoarthritis (OA) is the most frequent joint disease; however, the etiopathogenesis is still unclear. Chondrocytes rely primarily on glycolysis to meet cellular energy demand, but studies implicate impaired mitochondrial function in OA pathogenesis. The relationship between mitochondrial dysfunction and OA has been established. The aim of the study was to examine the differences in glucose and Fatty Acids (FA) metabolism, especially with regards to metabolic flexibility, in cybrids from healthy (N) or OA donors. Glucose and FA metabolism were studied using D-[¹⁴C(U)]glucose and [1-¹⁴C]oleic acid, respectively. There were no differences in glucose metabolism among the cybrids. Osteoarthritis cybrids had lower acid-soluble metabolites, reflecting incomplete FA β-oxidation but higher incorporation of oleic acid into triacylglycerol. Co-incubation with glucose and oleic acid showed that N but not OA cybrids increased their glucose metabolism. When treating with the mitochondrial inhibitor etomoxir, N cybrids still maintained higher glucose oxidation. Furthermore, OA cybrids had higher oxidative stress response. Combined, this indicated that N cybrids had higher metabolic flexibility than OA cybrids. Healthy donors maintained the glycolytic phenotype, whereas OA donors showed a preference towards oleic acid metabolism. Interestingly, the results indicated that cybrids from OA patients had mitochondrial impairments and reduced metabolic flexibility compared to N cybrids.

【 授权许可】

Unknown