Pro-inflammatory cytokines and adipose tissue

Abstract

Cytokines appear to be major regulators of adipose tissue metabolism. Therapeutic modulation of cytokine systems offers the possibility of major changes in adipose tissue behaviour. Cytokines within adipose tissue originate from adipocyte, preadipocyte and other cell types. mRNA expression studies show that adipocytes can synthesise both tumour necrosis factor a (TNF-a) and several interleukins (IL), notably IL-1b and IL-6. Other adipocyte products with ‘immunological’ actions include complement system products and macrophage colony-stimulating factor. Cytokine secretion within adipocytes appears similar to that of other cells. There is general agreement that circulating TNF-a and IL-6 concentrations are mildly elevated in obesity. Most studies suggest increased TNF-a mRNA expression or secretion in vitro in adipose tissue from obese subjects. The factors regulating cytokine release within adipose tissue appear to include usual ‘inflammatory‘ stimuli such as lipopolysaccaride, but also the size of the fat cells per se and catecholamines. There is conflicting data about whether insulin and cortisol regulate TNF-a. The effects of cytokines within adipose tissue include some actions that might be characterised as metabolic. TNF-a and IL-6 inhibit lipoprotein lipase, and TNF-a additionally stimulates hormone-sensitive lipase and induces uncoupling protein expression. TNF-a also down regulates insulin-stimulated glucose uptake via effects on glucose transporter 4, insulin receptor autophosphorylation and insulin receptor substrate-1. All these effects will tend to reduce lipid accumulation within adipose tissue. Other effects appear more ‘trophic’, and include the induction of apoptosis, regulation of cell size and induction of de-differentiation (the latter involving reduced peroxisome proliferator-activated receptor g). Cytokines are important stimulators and repressors of other cytokines. In addition, cytokines appear to modulate other regulatory systems. Examples of the latter include effects on leptin secretion (probably stimulation followed by inhibition) and reduction of b3-adrenoceptor expression. There seems to be no clear agreement as to which cytokines derived from adipose tissue act as remote regulators, i.e. hormones. Leptin, which is structurally a cytokine, is also a hormone. IL-6 appears to be released systemically by adipose tissue, but TNF-a is probably not. Both leptin and IL-6 appear to act on the hypothalamus, IL-6 acts on the liver, while leptin may have actions on the pancreas. The importance of the immune system in whole-body energy balance provides a rationale for the links between cytokines and adipose tissue. It seems clear that TNF-a is a powerful autocrine and paracrine regulator of adipose tissue. Other cytokines, notably leptin, and possibly IL-6, have lesser actions on adipose tissue. These cytokines act as hormones, reporting the state of adipose tissue stores throughout the body.

Low grade inflammation, as evidenced by basal high sensitivity CRP, is not correlated to outcome measures in IVF

“…White adipose tissue plays a central role in the low grade inflammatory state that is characteristic of obesity [25,26]. In fact, adipose tissue is a potent source of inflammatory interleukins and other circulating cytokines, the secretion of which increase with adiposity [25][26][27]. In agreement with previous studies [20,28], we have found a significant correlation between basal hs-CRP and BMI.…”

Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’

“…In this study we could not find any independent associations between plasma levels of TNF-α or IL-6 and fat cell size or insulin resistance. As suggested previously, these adipokines may have mainly paracrine effects [14,37].…”

Obesity increases the risk of UV radiation-induced oxidative stress and activation of MAPK and NF-κB signaling

“…It has been suggested that the increased oxidant stress that is associated with obesity may be due to the presence of excessive adiposity per se because adipocytes and preadipocytes have been identified as sources of inflammatory cytokines, including TNF-α, interleukin (IL)-1-β and IL-6 [34]. Cytokines are potent stimuli for the production of ROS/RNS by macrophages and monocytes [35]; therefore, we examined the effect of chronic UVB exposure on the secretion of pro-inflammatory cytokines.…”