The burden of metabolic syndrome on osteoarthritic joints

Abstract

BackgroundThe prevalence of osteoarthritis (OA) increases with obesity, with up to two thirds of the elderly obese population affected by OA of the knee. The metabolic syndrome (MetS), frequently associated with central obesity and characterised by elevated waist circumference, raised fasting plasma glucose concentration, raised triglycerides, reduced high-density lipoproteins, and/or hypertension, is implicated in the pathogenesis of OA. This narrative review discusses the mechanisms involved in the influence of MetS on OA, with a focus on the effects on macrophages and chondrocytes.Main textA skewing of macrophages towards a pro-inflammatory M1 phenotype within synovial and adipose tissues is thought to play a role in OA pathogenesis. The metabolic perturbations typical of MetS are important drivers of pro-inflammatory macrophage polarisation and activity. This is mediated via alterations in the levels and activities of the cellular nutrient sensors 5′ adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1), intracellular accumulation of metabolic intermediates such as succinate and citrate, and increases in free fatty acids (FFAs) and hyperglycaemia-induced advanced glycation end-products (AGEs) that bind to receptors on the macrophage surface. Altered levels of adipokines, including leptin and adiponectin, further influence macrophage polarisation. The metabolic alterations in MetS also affect the cartilage through direct effects on chondrocytes by stimulating the production of pro-inflammatory and catabolic factors and possibly by suppressing autophagy and promoting cellular senescence.ConclusionsThe influence of MetS on OA pathogenesis involves a wide range of metabolic alterations that directly affect macrophages and chondrocytes. The relative burden of intra-articular versus systemic adipose tissue in the MetS-associated OA remains to be clarified. Understanding how altered metabolism interacts with joints affected by OA is crucial for the development of further strategies for treating this debilitating condition, such as supplementing existing therapies with metformin and utilising ω-3 fatty acid derivatives to restore imbalances in ω-3 and ω-6 fatty acids.

β-Carotene Status Is Associated with Inflammation and Two Components of Metabolic Syndrome in Patients with and without Osteoarthritis

“…6 Hyperglycemia is defined as the level of fasting glucose ≥ 5.55 mmol/L (including use of hypoglycemic agents). 7 High triglycerides is defined as the level of triglycerides ≥ 1.70 mmol/L (including use of hypolipidemic agents). 8 Low HDL-C is defined as the level of HDL-C ≤ 1.04 mmol/L for males and ≤ 1.30 mmol/L for females.…”

Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

“…Recently, obesity has become a major cause of OA. 32 , 33 Thus, in the present study, we focused on obesity-associated OA in rats fed a high-fat diet (HFD). We hypothesized that curcumin may exert a chondroprotective effect by suppressing miR-34a, and thereby inhibiting apoptosis via upregulation of E2F1 and PITX1 and activating autophagy via the Akt/mTOR pathway.…”

Metformin: A Potential Therapeutic Tool for Rheumatologists

“…In particular, the metabolic perturbations typical of central obesity and metabolic syndrome (i.e., intracellular accumulation of succinate and citrate, increase in free fatty acids, hyperglycemia-induced AGEs) are important drivers of proinflammatory macrophage polarization and activity within synovial and adipose tissue, via alterations of AMPK and mTORC1, as well as of adipokine levels. This detrimental metabolic pattern also affects the cartilage through direct effects on chondrocytes [81]. Given the biological effects of metformin targeting the underlying OA pathogenic mechanisms, the drug might be considered a potential disease-modifying agent in the obese phenotype with knee OA, in addition to weight loss.…”