Prospects of potential adipokines as therapeutic agents in obesity-linked atherogenic dyslipidemia and insulin resistance

Abstract

Background: In normal circumstances, AT secretes anti-inflammatory adipokines (AAKs) which regulates lipid metabolism, insulin sensitivity, vascular hemostasis, and angiogenesis. However, during obesity AT dysfunction occurs and leads to microvascular imbalance and secretes several pro-inflammatory adipokines (PAKs), thereby favoring atherogenic dyslipidemia and insulin resistance. Literature suggests decreased levels of circulating AAKs and increased levels of PAKs in obesity-linked disorders. Importantly, AAKs have been reported to play a vital role in obesity-linked metabolic disorders mainly insulin resistance, type-2 diabetes mellitus and coronary heart diseases. Interestingly, AAKs counteract the microvascular imbalance in AT and exert cardioprotection via several signaling pathways such as PI3-AKT/PKB pathway. Although literature reviews have presented a number of investigations detailing specific pathways involved in obesity-linked disorders, literature concerning AT dysfunction and AAKs remains sketchy. In view of the above, in the present contribution an effort has been made to provide an insight on the AT dysfunction and role of AAKs in modulating the obesity and obesity-linked atherogenesis and insulin resistance.

Main body: "Obesity-linked insulin resistance", "obesity-linked cardiometabolic disease", "anti-inflammatory adipokines", "pro-inflammatory adipokines", "adipose tissue dysfunction" and "obesity-linked microvascular dysfunction" are the keywords used for searching article. Google scholar, Google, Pubmed and Scopus were used as search engines for the articles.

Conclusions: This review offers an overview on the pathophysiology of obesity, management of obesity-linked disorders, and areas in need of attention such as novel therapeutic adipokines and their possible future perspectives as therapeutic agents.

Keywords: Adipokines; Adipose tissue dysfunction; Anti-inflammatory adipokines; Atherogenic dyslipidemia; Insulin resistance; Metabolic disorder.

Fig. 1

Inflammatory adipokines suppress insulin signaling resulting in insulin resistance. IRS1/2 phosphorylated on specific tyrosine residues activates the phosphatidyl inositol 3-kinase (PI3K)-AKT/protein kinase B (PKB) pathway and Ras-mitogen-activated protein kinase (MAPK) pathway. PI3K-AKT signaling pathway regulates metabolic processes such as glucose uptake(muscle and adipocytes), glycogen synthesis (muscle and liver), protein synthesis(muscle and liver), and gluconeogenesis (liver). Inflammatory signals, TNF-a, IL-6, Leptin and saturated free fatty acid, activate inhibitory molecules such as SOCS and JNK to suppress insulin signaling resulting in insulin resistance. PI3K-dependent PDK1 activation is negatively regulated by phospholipid phosphatases such as phosphatase and tensin homolog (PTEN) that degrade PIP3 [86]. doi: 10.3389/fendo.2013.00071, Reproduced with permission Frontiers in Endocrinology)