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. 2013 Jun 12:4:71.
doi: 10.3389/fendo.2013.00071. eCollection 2013.

Adipokines mediate inflammation and insulin resistance

Hyokjoon Kwon  1 , Jeffrey E Pessin
Affiliations

Adipokines mediate inflammation and insulin resistance

Hyokjoon Kwon et al. Front Endocrinol (Lausanne). .

Abstract

For many years, adipose tissue was considered as an inert energy storage organ that accumulates and stores triacylglycerols during energy excess and releases fatty acids in times of systemic energy need. However, over the last two decades adipose tissue depots have been established as highly active endocrine and metabolically important organs that modulate energy expenditure and glucose homeostasis. In rodents, brown adipose tissue plays an essential role in non-shivering thermogenesis and in energy dissipation that can serve to protect against diet-induced obesity. White adipose tissue collectively referred too as either subcutaneous or visceral adipose tissue is responsible for the secretion of an array of signaling molecules, termed adipokines. These adipokines function as classic circulating hormones to communicate with other organs including brain, liver, muscle, the immune system, and adipose tissue itself. The dysregulation of adipokines has been implicated in obesity, type 2 diabetes, and cardiovascular disease. Recently, inflammatory responses in adipose tissue have been shown as a major mechanism to induce peripheral tissue insulin resistance. Although leptin and adiponectin regulate feeding behavior and energy expenditure, these adipokines are also involved in the regulation of inflammatory responses. Adipose tissue secretes various pro- and anti-inflammatory adipokines to modulate inflammation and insulin resistance. In obese humans and rodent models, the expression of pro-inflammatory adipokines is enhanced to induce insulin resistance. Collectively, these findings have suggested that obesity-induced insulin resistance may result, at least in part, from an imbalance in the expression of pro- and anti-inflammatory adipokines. Thus we will review the recent progress regarding the physiological and molecular functions of adipokines in the obesity-induced inflammation and insulin resistance with perspectives on future directions.

Keywords: adipocyte; adipokine; inflammation; insulin; macrophages and metabolism.

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Figures

Figure 1
Figure 1
Inflammatory adipokines suppress insulin signaling resulting in insulin resistance. IRS1/2 phosphorylated on specific tyrosine residues activates the phosphatidylinositol 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-α, IL-6, LPS, 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.
Figure 2
Figure 2
Altered composition of immune cells with obesity regulates the inflammatory responses in adipose tissue. Alternatively activated M2 macrophages, Th2 CD4+ T cells, regulatory CD4+ T cells (Treg), eosinophils, and iNKT cells are dominant immune cells in adipose tissue of lean mice. These cells secrete anti-inflammatory cytokines such as IL-4 and IL-10 to suppress inflammation and maintain insulin sensitivity in adipose tissue. In obese mice, the composition of immune cells is dynamically shifted to enhance inflammatory responses in adipose tissue. Classically activated M1 macrophages, Th1 CD4+ T cells, effector CD8+ T cells, mast cells, B cells, and neutrophils are increased and produce inflammatory mediators such as TNF-α, IFN-γ, autoantibodies, and elastase resulting in insulin resistance.
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