The role of adipokines in chronic inflammation

Abstract

Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function.

Keywords: adipose tissue; calorie restriction; chronic low-grade inflammation; infection; macrophage; obesity; type 2 diabetes.

Figure 1

Effects of calorie restriction and obesity on adipose tissue leukocyte populations, adipokine secretion, and chronic inflammation. Notes: Calorie restriction: VAT and SCAT adipocyte size declines but BMAT increases. Increased anti-inflammatory adipokines with greater risk of infectious disease. Lean state: IL-4, IL-13, IL-10 and TGF-b maintain M2 macrophage phenotype with normal metabolic and immune homeostasis. Obese state: hypertrophy promotes rarefaction and apoptosis. M1 macrophages engulf necrotic adipocytes forming crown-like structures. Proinflammatory cytokines and adipokines promote inflammation and diseases associated with obesity. Abbreviations: BMAT, bone marrow adipose tissue; T2D, type 2 diabetes; NAFLD, nonalcoholic fatty liver disease; SCAT, subcutaneous adipose tissue; VAT, visceral adipose tissue; Eos, eosinophils.