Resolution of inflammation: therapeutic potential of pro-resolving lipids in type 2 diabetes mellitus and associated renal complications

Abstract

The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) and its associated complications is increasingly recognized. The resolution of inflammation is actively regulated by endogenously produced lipid mediators such as lipoxins, resolvins, protectins, and maresins. Here we review the potential role of these lipid mediators in diabetes-associated pathologies, specifically focusing on adipose inflammation and diabetic kidney disease, i.e., diabetic nephropathy (DN). DN is one of the major complications of T2DM and we propose that pro-resolving lipid mediators may have therapeutic potential in this context. Adipose inflammation is also an important component of T2DM-associated insulin resistance and altered adipokine secretion. Promoting the resolution of adipose inflammation would therefore likely be a beneficial therapeutic approach in T2DM.

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease

“…Adipose inflammation appears to be the common denominator of obesity-related pathologies (Donath and Shoelson, 2011; McNelis and Olefsky, 2014). Promoting the resolution of adipose inflammation is therefore a potential therapeutic approach that could alleviate obesity-associated organ dysfunction (Borgeson and Godson, 2012; Claria et al, 2012; Donath, 2014; Donath et al, 2013; Spite et al, 2014; Tabas and Glass, 2013). The results presented here demonstrate that LXA 4 attenuates obesity8 associated adipose inflammation and thereby alleviates liver and kidney diseases associated with obesity.…”

“…Immunomodulation and specifically immunoresolvents are suggested as a therapeutic strategy to overcome chronic inflammation and disease (Borgeson and Godson, 2012; Donath, 2014; Donath et al, 2013; Serhan, 2007; Serhan and Savill, 2005; Tabas and Glass, 2013). Acute inflammation is orchestrated in part by chemical autacoids in the form of peptides (cytokines, chemokines) and lipid mediators ( i.e .…”

The role of lipoxins in cardiometabolic physiology and disease

“…As outlined in the introduction, prolonged obesity causes a state of systemic low-grade inflammation, resulting in insulin resistance, metabolic syndrome, and pathologies such as T2DM, atherosclerosis, and nonalcoholic fatty liver disease [118]. As detailed below, LXs promotes resolution of adipose inflammation and protects against obesity-induced metabolic disease (for reviews see [17,40,51]). Importantly, the FPR2/ALX receptor is expressed in both human and mouse adipose tissue [57,119].…”

“…Impaired inflammatory resolution may underlie the pathogenesis of chronic inflammatory disorders, such as metabolic syndrome, diabetes, and CVD [45,46]. The therapeutic potential of using SPMs to promote resolution and overcome chronic inflammation and disease has therefore been highlighted [8,19,43,[47][48][49][50][51].…”

Elevated toll-like receptor 3 inhibits pancreatic β-cell proliferation through G1 phase cell cycle arrest

“…Type 2 diabetes mellitus (DM) is a typical metabolic disease with systemic inflammation (Hotamisligil, 2006;Nakamura et al, 2010;Hotamisligil and Erbay, 2008;Stefanov et al, 2012;Börgeson and Godson, 2012;Rodgers et al, 2012). As a major risk factor for the development of type 2 DM, obesity can trigger a chronic, low-grade local inflammation in metabolic tissues, termed metaflammation (Hotamisligil, 2006;Nakamura et al, 2010).…”