Macrophage infiltration and cytokine release in adipose tissue: Angiogenesis or inflammation?

Diabetology International 11/2010; 1(1):26-34. DOI: 10.1007/s13340-010-0003-x


The observation that obese adipose tissue was infiltrated by macrophages triggered the concept that type 2 diabetes is a low-grade
inflammatory disease. In this review, we re-evaluate the role of macrophage infiltration, TNFα secretion and IKKβ/JNK signalling
in insulin resistance, and put forward the hypothesis that these intermediates are important mediators of adipose tissue angiogenesis.
Expansion of adipose tissue vasculature is essential to support adipose tissue growth during development and adipose tissue
expansion in adulthood. We propose that a major role of so-called pro-inflammatory adipokines is to stimulate adipose tissue
angiogenesis to support the nutrient requirements of expanding fat depots. Inhibition of angiogenesis overrides insulin resistance
and obesity not by blocking the peripheral effects of the inflammatory pathway on insulin resistance, but rather by central
effects on food intake. This unveils a possible feedback loop involving adipose angiogenesis and central regulation of food
intake that is independent of a classical immune response.

KeywordsAngiogenesis-Macrophages-Inflammation-Adipose tissue-Insulin resistance-Adipokines

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Available from: Lindsay E Wu, May 08, 2014
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    ABSTRACT: The prevalence of type 2 diabetes is evolving globally at an alarming rate. This fact is mainly the result of our global lifestyle "modernization" that has resulted in overweight and obesity. Dysfunction of peroxisome proliferator activated receptor-gamma (PPAR-gamma) has been implicated in the development of insulin resistance, while a reduce expression of many PPAR-gamma regulated genes has been observed in an obese diabetic state. Thiazolidinediones (TZDs) are potent exogenous agonists of PPAR-gamma, which augment the effects of insulin to its cellular targets and mainly at the level of adipose tissue. Preclinical and clinical studies have demonstrated that apart from their glucose-lowering activity, these drugs also regulate the production of inflammatory mediators by cells that play a pivotal role in the pathogenesis of atherosclerosis. This paper summarizes the evolving changes observed in an enlarged adipose tissue and examines the activity of TZDs in their main cellular targets. It also discusses whether these cellular pleiotropic effects can result in a clinically meaningful outcome, in terms of cardiovascular benefit, in this population.
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