Invited ReviewInflammation as a link between obesity, metabolic syndrome and type 2 diabetes
Introduction
Obesity, in particular excess visceral adiposity, is associated with insulin resistance, hyperglycaemia, dyslipidaemia and hypertension, which together are termed “metabolic syndrome” [1]. These metabolic disorders increase the risk of development of type 2 diabetes mellitus (T2DM) and cardiovascular diseases and contribute to high rates of mortality and morbidity [1]. T2DM is the most prevalent metabolic disease in the world and is characterized by defects in insulin secretion and a peripheral insulin resistance in the skeletal muscle, the adipose tissue and the liver. The progression from obesity-related insulin resistance to T2DM remains poorly understood but implicates a failure of pancreatic β-cells to compensate for insulin resistance leading to chronic hyperglycaemia. A chronic low-grade inflammation and an activation of the immune system are observed in abdominal obesity and may have a role in the pathogenesis of obesity-related metabolic disorders [2], [3], [4], [5]. This review summarizes data implicating the immune system in the pathophysiogy of insulin resistance and T2DM. We will also examine the biological, tissular and cellular inflammatory markers associated with obesity-related metabolic disorders that may predict the development of T2DM. Molecular mechanisms underlying this inflammatory activation state will be reviewed and preliminary results obtained with anti-inflammatory therapies in the prevention and treatment of T2DM will be described.
Section snippets
Inflammatory markers in obesity, metabolic syndrome and T2DM
White blood cell counts and plasma levels of coagulation factors (fibrinogen and plasminogen activator inhibitor 1 (PAI-1)), acute-phase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA), pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6), and chemokines are elevated in obese and T2DM patients and shown to be reduced when these patients are engaged in a more intensive lifestyle causing weight loss [6], [7], [8], [9], [10], [11]. These
Tissue inflammation in obesity and T2DM
A number of experimental and clinical data have clearly established that adipose tissue, liver, muscle and pancreas are sites of inflammation in presence of obesity and T2DM. An infiltration of macrophages into these tissues is seen in animal models of obesity and diabetes as well as in obese human individuals with metabolic syndrome or T2DM. These cells are crucial for the production of pro-inflammatory cytokines [4], including TNFα, IL-6 and IL-1β. They act in an autocrine and paracrine
Sensors and mediators of inflammation in obesity and T2DM
Although subclinical inflammation is important in the pathogenesis of T2DM, the events initiating this inflammatory process remain unclear and could involve different but synergic mechanisms leading to the activation of NF-κB and JNK pathways, cytokines and chemokines release and recruitment of immune cells.
Anti-inflammatory therapeutic perspectives
Given the obvious link between inflammation and pathogenesis of T2DM, anti-inflammatory strategies have been proposed for its prevention and treatment. They are extensively reviewed elsewhere [66].
Conclusions
The concept of T2DM as an inflammatory disease has recently emerged and seems to be confirmed by accumulating evidences. A number of studies have shown that abdominal obesity is associated with systemic low grade inflammation leading to insulin resistance and metabolic disorders. Moreover, systemic inflammatory markers can predict development of T2DM and cardiovascular diseases in the general population, and should be therefore used more widely in clinical practice to detect individuals at
Conflict of interest statement
None declared.
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