@Article{,
AUTHOR = {Jean-Philippe Bastard, Mustapha Maachi, Claire Lagathu, Min Ji Kim, Martine Caron, Hubert Vidal, Jacqueline Capeau, Bruno Feve},
TITLE = {Recent advances in the relationship between obesity, inflammation, and insulin resistance},
JOURNAL = {European Cytokine Network},
VOLUME = {17},
YEAR = {2006},
NUMBER = {1},
PAGES = {4--12},
URL = {http://www.techscience.com/ECN/v17n1/66162},
ISSN = {1952-4005},
ABSTRACT = {It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of
white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can
subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site
of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous
physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and
secretion of a wide range of inflammatory molecules including TNF-α and interleukin-6 (IL-6), which may have
local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT
is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines.
Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an
improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but
also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are
overproduced during obesity, including leptin, TNF-α, IL-6 and resistin. Conversely, expression and plasma levels
of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-α
production and macrophage activation. TNF-α is overproduced in adipose tissue of several rodent models of
obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual
involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human
adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of
cardiovascular complications. Both TNF-α and IL-6 can alter insulin sensitivity by triggering different key steps
in the insulin signalling pathway. In rodents, resistin can induce insulin resistance, while its implication in the
control of insulin sensitivity is still a matter of debate in humans. Adiponectin is highly expressed in WAT, and
circulating adiponectin levels are decreased in subjects with obesity-related insulin resistance, type 2 diabetes and
coronary heart disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid oxidation in skeletal
muscle. In addition, adiponectin counteracts the pro-inflammatory effects of TNF-α on the arterial wall and
probably protects against the development of arteriosclerosis. In obesity, the pro-inflammatory effects of cytokines
through intracellular signalling pathways involve the NF-κB and JNK systems. Genetic or pharmacological
manipulations of these effectors of the inflammatory response have been shown to modulate insulin sensitivity in
different animal models. In humans, it has been suggested that the improved glucose tolerance observed in the
presence of thiazolidinediones or statins is likely related to their anti-inflammatory properties. Thus, it can be
considered that obesity corresponds to a sub-clinical inflammatory condition that promotes the production of
pro-inflammatory factors involved in the pathogenesis of insulin resistance.},
DOI = {}
}