Oleate prevents palmitate-induced mitochondrial dysfunction in chondrocytes

Abstract

BACKGROUND : The clear association between obesity and osteoarthritis (OA) in joints not subjected to mechanical overload, together with the relationship between OA and metabolic syndrome (MS), suggests that there are systemic factors related to metabolic disorders that are involved in the metabolic phenotype of OA. The aim of this work is to study the effects of palmitate (PA) and oleate (OL), as the most abundant fatty acids (FA) present in the diet and serum, on cellular metabolism in an " in vitro " model of human chondrocytes. METHODS :.The Seahorse XF96 Analyzer was used tomeasure the mitochondrial, glycolytic function and the contribution of the mitochondrial oxidative phosphorilation system (OXPHOS) and glycolysis to the production of ATP, in the T/C-28a2 chondrocyte treated with to PA, OL and palmitate/oleate (PA/OL) ratio 1:2. Subsequently ATP bioluminescence assay kit was used for ATP quantification. To detect the presence of lipid droplets, two types of stains were performed and the amount of Triglycerides was quantified spectrophotometrically. RESULTS : PA, but not OL, produces mitochondrial dysfunction observed with a lower rate of OCR intended for the synthesis of ATP, coupling efficiency, maximal respiration and spare respiratory capacity. Glycolytic function showed lower rates for both glycolytic capacity and glycolytic reserve when cells were incubated withFA in relation to basal condition (BC). The production rate of ATP from OXPHOS showed lower values in chondrocytes incubated with any of the FAs. The evaluation of possible formation of Lipid droplets (LD) showed a significant increase of these structures in FA conditions, being significantly higher when the cells were incubated with OL. CONCLUSIONS : PA and OL show antagonistic effects in human chondrocytes; while increased levels of PA induce mitochondrial dysfunction and hinder the response of chondrocytes through the glycolytic pathway, OL shows a cytoprotective effect through which promotes the formation of triglycerides-rich LD, as well as the incorporation of PA.

Oleate Prevents Palmitate-Induced Mitochondrial Dysfunction in Chondrocytes

“…The content of the manuscript have previously appeared as an online preprint ( Vaquez-Mosquera et al, 2020 ).…”