Targeting macrophage polarization for therapy of diabesity–the feasibility of early improvement of insulin sensitivity and insulin resistance-a comprehensive systematic review

Abstract

The incidence of obesity is increasing in mammoth proportions so much so that associated comorbidity T2DM incidence is increasing markedly that we had to coin a term “Diabesity” to target both together. Earlier trying to review etiopathogenesis of both obesity and type 2 DM we found that whatever drugs that are formulated usually do not work with some complications and till now other than bariatric surgery we have no permanent cure for long term maintenance. Further T2DM might be a disease of 2 etiopathogenesis, namely inflammatory, as well as metabolic. Although metabolic inflammation has the properties of being systemic, their common initiating point is tissue resident macrophages, whose successful physiological or abnormal pathological adaptation to its microenvironment dictates disease course as well as severity. Earlier we reviewed macrophage polarization in case of nonalcoholic fatty liver disease (NAFLD). Here we review it more comprehensively regarding crucial modes, of macrophage polarization, inflammatory, as well as non inflammatory which sees to the formation of insulin resistance (IR) as well as type 2 diabetes mellitus (T2DM). Details of macrophage polarization, bioenergetics macrophage adaptations in different scenario is discussed in detail along with role of transcription factors like interferon regulatory factor 5 (IRF5), nuclear factor kappa B (NFKB), toll like receptor 4 (TLR4), liver X receptor (LXR), activator protein 1(AP1), hypoxia inducible factor 1 (HIF1), signal transducers and activators of transcription (STATS) in all these signaling besides peroxisome proliferator activated receptor (PPAR).