Abstract
Obesity-associated chronic tissue inflammation is a key contributing factor to type 2 diabetes mellitus, and a number of studies have clearly demonstrated that the immune system and metabolism are highly integrated. Recent advances in deciphering the various immune cells and signaling networks that link the immune and metabolic systems have contributed to our understanding of the pathogenesis of obesity-associated inflammation. Other recent studies have suggested that pattern recognition receptors in the innate immune system recognize various kinds of endogenous and exogenous ligands, and have a crucial role in initiating or promoting obesity-associated chronic inflammation. Importantly, these mediators act on insulin target cells or on insulin-producing cells impairing insulin sensitivity and its secretion. Here, we discuss how various pattern recognition receptors in the immune system underlie the etiology of obesity-associated inflammation and insulin resistance, with a particular focus on the TLR (Toll-like receptor) family protein Radioprotective 105 (RP105)/myeloid differentiation protein-1 (MD-1).
Highlights
Obesity has become a worldwide health problem because it is strongly associated with metabolic syndromes including type 2 diabetes mellitus (T2DM), atherosclerosis and ischemic heart diseases [1,2].Accumulating evidence indicates that chronic-low grade inflammation has a crucial role in the pathogenesis of obesity-related metabolic dysfunction [3,4]
As analysis of Radioprotective 105 (RP105)/myeloid differentiation protein-1 (MD-1) expression has been largely restricted to the immune system, we have examined whether RP105/MD-1 has a role in sensing an obesity-related endogenous ligand or whether this complex participates in immune responses leading to diet-induced adipose tissue inflammation and insulin resistance [37,84]
Using a co-culture system composed of 3T3-L1 adipocytes and macrophage cell lines, we have shown that RP105 and MD-1
Summary
Obesity has become a worldwide health problem because it is strongly associated with metabolic syndromes including type 2 diabetes mellitus (T2DM), atherosclerosis and ischemic heart diseases [1,2]. Recent studies have suggested that excessive amounts of DAMPs induce chronic low-grade inflammation in various tissues, including adipose tissue, islets and CNS [34]. These responses are mediated, at least in part, by the activation of PRRs. In addition, IL-1β has been implicated in various non-microbial pro-inflammatory diseases, including atherosclerosis, gout, and T2DM [35]. We recently identified the Radioprotective 105 (RP105)/myeloid differentiation (MD)-1 complex as a key regulator of diet-induced chronic inflammation in adipose tissue, obesity and insulin resistance that appear to be independent of the TLR4-dependent pathway [37]. We will overview our recent research regarding RP105/MD-1 and discuss potential mechanisms by which RP105/MD-1 is involved in chronic adipose tissue inflammation
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