TNFα expression of subcutaneous adipose tissue in obese and morbid obese females: relationship to adipocyte LPL activity and leptin synthesis

Abstract

INTRODUCTION:Tumor necrosis factor (TNFa) has been invoked as an adipostat. Accordingly, the adipose tissue expression of TNFa has been shown to be proportional to the degree of adiposity. The regulatory role of TNFa in obesity may be controlled by several mechanisms. These include the inhibitory effect on LPL activity, the mediation on glucose homeostasis or the effect on leptin. To assess the role of TNFa in obesity we measured adipocyte TNFa expression in 96 females with a wide range of adiposity and with or without type 2 diabetes. We analysed the relationship between TNFa expression, adipocyte LPL activity, insulin resistance and leptin in this population. RESULTS: The TNFa and leptin expression of the adipose tissue in obese and morbid obese patients were significantly higher than in controls. Obese and morbid obese patients had slightly higher levels of LPL activity, but these differences were not significant. We observed a significant relationship between adipose TNFa expression and body mass index (r ¼ 0.35, P < 0.001). TNFa expression was negatively related to LPL activity (r ¼ 7 0.28, P < 0.05) and positively related to leptin expression (r ¼ 0.35, P < 0.001). CONCLUSION: Our results indicate that obese women, even those with morbid obesity, over-express TNFa in subcutaneous adipose tissue in proportion to the magnitude of the fat depot and independently of the presence of type 2 diabetes. The TNFa system may be a homeostatic mechanism that prevents further fat deposition by regulating LPL activity and leptin production.

Inflammation, obesity and comorbidities: the role of diet

“…Plasma levels of TNF are persistently elevated in obese or type 2 diabetic patients and among patients at increased risk of recurrent coronary events 9,21 . Its role favoring insulin resistance is mediated by the increase in adipocyte lipolysis 22 and through its role on insulin receptor substrate-1 phosphorylation and modulating glucose transporter type 4 (GLUT4) activity 23 .…”

“…This overexpression could explain at least a part of the atherogenic and cardiovascular risk associated obesity. White adipose tissue is also specially characterised by the production and secretion of more than 50 adipokines, such as leptin, tumour necrosis factor (TNF) or interleukin-6 (IL6) with characterised local and systemic pro-inflammatory effects 2,8,9 . Several of these molecules are over released into the circulation in obese subjects leading to a low grade of chronic systemic inflammation.…”

Fat poetry: a kingdom for PPARγ

“…Thus, it is the macrophage-produced TNF-α that is responsible for the systemic effects [86]. Although there is no clear correlation between obesity and insulin resistance versus levels of plasma TNF-α, expression of this cytokine in WAT correlates with these two pathologies [87,88]. Chronic exposure of mice to TNF-α induces insulin resistance, decreases the expression of genes involved in adipogenesis and lipogenesis in WAT, and promotes lipolysis, while deletion of the TNF-α gene improves circulating FFA and insulin sensitivity in mouse obesity [89].…”

Virgin olive oil in preventive medicine: From legend to epigenetics

“…They also release cytokines with typical pro-inflammatory activities including leptin, the MCP-1, the tumor necrosis factor-alpha (TNFalpha), and the interleukin-6 (IL-6), thereby promoting a state of chronic inflammation, as shown by the abundant number of macrophages secreted in circulation by white adipose tissue. They also release free fatty acids and glycerol, promoting resistance to insulin, and leading to type 2 diabetes and metabolic syndrome, although the mechanisms behind this remain uncharacterized [80,81,[82][83][84][85][86]. They are consistently elevated in obese subjects and in type 2 diabetes in subjects with a high risk of coronary heart disease and rheumatoid arthritis, leading to an increase in lipolysis and lipid oxidation [80,[82][83][84][87][88][89].…”

“…They also release free fatty acids and glycerol, promoting resistance to insulin, and leading to type 2 diabetes and metabolic syndrome, although the mechanisms behind this remain uncharacterized [80,81,[82][83][84][85][86]. They are consistently elevated in obese subjects and in type 2 diabetes in subjects with a high risk of coronary heart disease and rheumatoid arthritis, leading to an increase in lipolysis and lipid oxidation [80,[82][83][84][87][88][89]. It should also be noted that the stimulation to produce pro-inflammatory adipokines during the growth phase of white fat tissue is determined by a condition of local hypoxia that leads to increased expression of genes induced by hypoxia such as vascular endothelial growth factor (VEGF), erythropoietin (EPO) and hypoxia inducible factor-1 (HIF-1).…”