Accumulation of Oxidized LDL in the Tendon Tissues of C57BL/6 or Apolipoprotein E Knock-Out Mice That Consume a High Fat Diet: Potential Impact on Tendon Health

Abstract

ObjectiveClinical studies have suggested an association between dyslipidemia and tendon injuries or chronic tendon pain; the mechanisms underlying this association are not yet known. The objectives of this study were (1) to evaluate the impact of a high fat diet on the function of load-bearing tendons and on the distribution in tendons of oxidized low density lipoprotein (oxLDL), and (2) to examine the effect of oxLDL on tendon fibroblast proliferation and gene expression.MethodsGene expression (Mmp2, Tgfb1, Col1a1, Col3a1), fat content (Oil Red O staining), oxLDL levels (immunohistochemistry) and tendon biomechanical properties were examined in mice (C57Bl/6 or ApoE -/-) receiving a standard or a high fat diet. Human tendon fibroblast proliferation and gene expression (COL1A1, COL3A1, MMP2) were examined following oxLDL exposure.ResultsIn both types of mice (C57Bl/6 or ApoE -/-), consumption of a high fat diet led to a marked increase in oxLDL deposition in the load-bearing extracellular matrix of the tendon. The consumption of a high fat diet also reduced the failure stress and load of the patellar tendon in both mouse types, and increased Mmp2 expression. ApoE -/- mice exhibited more pronounced reductions in tendon function than wild-type mice, and decreased expression of Col1a1 compared to wild type mice. Human tendon fibroblasts responded to oxLDL by increasing their proliferation and their mRNA levels of MMP2, while decreasing their mRNA levels for COL1A1 and COL3A1.ConclusionThe consumption of a high fat diet resulted in deleterious changes in tendon function, and these changes may be explained in part by the effects of oxLDL, which induced a proliferative, matrix-degrading phenotype in human tenocytes.

Paternal Resistance Training Modulates Calcaneal Tendon Proteome in the Offspring Exposed to High-Fat Diet

“…Previous data reported detrimental effects of HF diet on tendon biomechanical and morphological properties (Boivin et al, 2013;Grewal et al, 2014). Diet switch from HF diet to lowfat diet seems to resolve metabolic dysfunction, but it was not able to reverse tendinopathic changes (Studentsova et al, 2018).…”

“…In animal models, consumption of high-fat (HF) diet promotes deleterious effects on morphological, biomechanical and biochemical properties of tendons (Biancalana et al, 2010;Boivin et al, 2013). Previous data have shown that rats exposed to HF diet displayed an increase of oxidized lowdensity lipoprotein deposition in extracellular matrix (ECM) as well a reduction of failure stress in the patellar tendon when compared with rats exposed to a standard diet (Grewal et al, 2014). Zucker rats displayed disorganized collagen fibril bundles and decreased average fibril diameter accompanied by adverse effects in displacement at maximum load and maximum strain, indicating a significant harmful ECM remodeling in deep digital flexor tendon (Biancalana et al, 2010).…”

Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

“…Apolipoprotein E is required for normal catabolism and clearance of lipoprotein constituents and acts as a ligand for cell-surface LDL receptors. Therefore, apoE-knockout mice (apoE (−/−) ) experience a severe, progressive form of hypercholesterolemia, making them the most commonly employed model for studying the adverse influence of cholesterol on various body [ 30 ]. NAFLD, affecting up to a third of the population in many developed countries [ 31 ], has recently attracted considerable attention worldwide.…”

Lipids, adiposity and tendinopathy: is there a mechanistic link? Critical review

“…We recently conducted a study on mice to examine the influences of localised lipid (within or around the tendon tissue) versus systemic lipid (hypercholesterolaemia) on tendon biomechanical properties. 48 Two strains of mice (normal mice or mice predisposed to developing hypercholesterolaemia, the apolipoprotein E knockout (ApoE-KO) model) were fed a normal diet, or a high-fat diet. Interestingly, the accumulation of adipose tissue around tendons occurred in normal mice that were fed a high-fat diet, and their tendons demonstrated a significant reduction in failure load and stress compared with mice on a normal diet.…”