Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin

Abstract

Adipose tissue is an active endocrine organ, and our knowledge of this secretory tissue, in recent years, has led us to completely rethink how our body functions and becomes dysregulated with weight gain. Human adipose tissue appears to act as a multifunctional secretory organ with the capacity to control energy homoeostasis through peripheral and central regulation of energy homoeostasis. It also plays an important role in innate immunity. However, the capability to more than double its original mass to cope with positive energy balance in obesity leads to many pathogenic changes. These changes arise within the adipose tissue as well as inducing secondary detrimental effects on other organs like muscle and liver, including chronic low-grade inflammation mediated by adipocytokines (adipokine inflammation). This inflammation is modulated by dietary factors and nutrients including glucose and lipids, as well as gut bacteria in the form of endotoxin or LPS. The aim of this current review is to consider the impact of nutrients such as glucose and lipids on inflammatory pathways, specifically within adipose tissue. Furthermore, how nutrients such as these can influence adipokine inflammation and consequently insulin resistance directly through their effects on secretion of adipocytokines (TNFa, IL6 and resistin) as well as indirectly through increases in endotoxin is discussed.

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

“…Several factors such as oxidative stress, inflammation, glucotoxicity, lipotoxicity and adipokine dysregulation have been implicated in the genesis of insulin resistance (Shoelson et al 2007;Piya et al 2013). Inflammatory cytokines have been shown to play an important role in the regulation of glucose homeostasis and insulin resistance.…”

Obesity and thyroid cancer

“…Leptin is another adipokine predominantly secreted by adipose tissue, although it can also be produced by skeletal muscle, stomach, and plasma (Piya et al 2013). Leptin is structurally similar to other cytokines, such as IL2, IL6, and granulocyte-colony-stimulating factor (G-CSF), a characteristic that makes leptin capable of participating in similar cellular and organic processes, such as the control of food intake through satiety sensation, regulation of energy expenditure, the activation of monocytes and macrophages, stimulation of VEGF, angiogenesis, cell proliferation, and the suppression of anti-inflammatory cytokines (Kwon & Pessin 2013).…”

“…Its name is derived from the fact that it was primarily related to IR by the suppression of insulinmediated signaling in rat adipocytes (Steppan et al 2005), but in humans this association is not always present. Actually, in humans, resistin has diverse functions in proliferative, anti-apoptotic, pro-inflammatory, and proangiogenic events (Hlavna et al 2011, Piya et al 2013. Inflammatory cytokines such as IL1b, IL6, TNFa, and LPS may induce resistin expression, but, conversely, resistin has been demonstrated to stimulate the production of IL6 and TNFa through the NFkB signaling pathway (Bokarewa et al 2005).…”

The Impact of Neutrophil Proteinase 3 on IGFBP-3 Proteolysis in Obesity

“…Although it is generally established that low-grade adipose tissue inflammation contributes substantially to the burden of IR, the pathophysiology underlying the development of IR is complex and multifactorial [8]. Thus, a clearer understanding of the mechanisms leading to obesity-associated IR is necessary to identify novel targets for the prevention and treatment of many IR-driven conditions such as T2DM.…”

“…The endocrine paradigm suggests that visceral fat in obesity, consisting primarily of adipocytes, secretes various pro-inflammatory adipokines such as tumor necrosis factor (TNF), leptin, visfatin, resistin, and interleukin (IL)-6 creating a state of local thus accelerating events leading to systemic IR, T2DM and metabolic syndrome. Recent studies have further identified that obesity-induced inflammatory adipokines/cytokines interfere with insulin signaling in visceral adipocytes by decreasing the levels of insulin receptor substrate-1 (IRS-1), glucose transporter-4 (GLUT4) and adiponectin leading to a state of IR via autocrine/paracrine influences [4,[8][9][10][11][12].…”