Inflammatory mechanisms linking obesity and tendinopathy

Abstract

Chronic tendinopathy is a debilitating tendon disorder with disappointing treatment outcomes. This review focuses on the potential roles of chronic low-grade inflammation in promoting tendinopathy in obesity. A systematic literature search was performed to identify all clinical studies supporting the actions of obesity-associated inflammatory mediators in the development of tendinopathy. The mechanisms of obesity-induced chronic inflammation in adipose tissue are firstly reviewed. Common inflammatory mediators potentially linking obesity and the development of tendinopathy, and their association with mechanical overuse, are discussed, along with pre-clinical evidences and a systematic literature search on clinical studies. The potential contribution of local adipose tissues in the promotion of inflammation, pain and tendon degeneration is then discussed. The future research directions are proposed.

Translational potential statement: Better understanding of the roles of obesity-associated inflammatory mediators on tendons will clarify the pathophysiological drivers of tendinopathy in patients with obesity and identify possible treatment targets. Further studies on the mechanisms of obesity-induced chronic inflammation on tendon are a promising direction for the treatment of tendinopathy.

Keywords: Adipose tissue; Inflammation; Obesity; Tendinopathy; Tendon overuse.

Fig. 1

Schematic diagrams summarizing the initiators and mediators of obesity-induced systemic chronic low-grade inflammation. Under healthy condition, the immune cells maintain an anti-inflammatory type 2 environment and polarize the resident adipose tissue macrophages to an M2 state. In obesity, the increase of bacterial LPS, adipocyte hypertrophy, hyperplasia, hypoxia, ER stress, UPR and adipocyte necrosis induces the release of adipokines, FFA, alarmins, glucose and lactate. Immune cells exhibiting a type 1 inflammatory phenotype are recruited to the adipose tissue in response to various inflammatory signals and chemokines. Macrophages, the key effectors of the complex type 1 immune response triggered by various immune cell types, are polarized to a pro-inflammatory M1 phenotype. The release of the adipokines, FFA, alarmins, glucose and lactate to the circulation creates a systemic chronic low-grade inflammatory milieu which causes various obesity-associated comorbidities.

Fig. 2

Schematic diagram summarizing the common inflammatory mediators potentially linking obesity and the development of tendinopathy. Many common inflammatory mediators of obesity and tendinopathy are also mechano-sensitive, supporting that obesity may reduce the capacity of tendon to resolve inflammation and tolerate load, and amplify the deleterious effect of tendon overuse. The immune cells are chemoattracted to tendon, triggering further inflammatory responses and tendon damages. People with obesity can have fat accumulation in muscles and tendons. The accumulation of fat in tendons disrupts its integrity. Muscle dysfunction due to fat deposition may also indirectly affect tendon function. Besides the visceral and subcutaneous fat depots, fatty deposition in pathological muscles and tendons as well as fat pads adjacent to tendons can be local sources of adipose tissue-associated inflammatory mediators. The metabolic effects associated with systemic obesity therefore can extend to the local fat tissues, which can promote inflammation, pain, and tendon degeneration, contributing to the development and progression of tendinopathy.