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JNKs, insulin resistance and inflammation: A possible link between NAFLD and coronary artery disease.

Abstract：

:The incidence of obesity has dramatically increased in recent years. Consequently, obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem. Therefore, the contribution of adipose tissue to metabolic homeostasis has become a focus of interest. In this review, we discuss the latest discoveries that support the role of lipids in nonalcoholic fatty liver disease. We describe the common mechanisms (c-Jun amino-terminal kinases, endoplasmic reticulum stress, unfolded protein response, ceramide, low-grade chronic inflammation) by which lipids and their derivatives impair insulin responsiveness and contribute to inflammatory liver and promote plaque instability in the arterial wall. Presenting the molecular mechanism of lipid activation of pro-inflammatory pathways, we attempt to find a link between nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular diseases. Describing the common mechanisms by which lipid derivatives, through modulation of macrophage function, promote plaque instability in the arterial wall, impair insulin responsiveness and contribute to inflammatory liver and discussing the molecular mechanism of lipid activation of pro-inflammatory pathways, the key roles played by the proliferator-activated receptor and liver X receptor α, nuclear receptors-lipid sensors that link lipid metabolism and inflammation, should be emphasized. Further studies are warranted of anti-inflammatory drugs such as aspirin, anti-interleukin-6 receptors, immune-modulators (calcineurin inhibitors), substances enhancing the expression of heat shock proteins (which protect cells from endoplasmic reticulum stress-induced apoptosis), and anti- c-Jun amino-terminal kinases in well-designed trials to try to minimize the high impact of these illnesses, and the different expressions of the diseases, on the whole population.

journal_name

World J Gastroenterol

journal_title

World journal of gastroenterology

authors

Tarantino G,Caputi A

doi

10.3748/wjg.v17.i33.3785

subject

Has Abstract

pub_date

2011-09-07 00:00:00

pages

3785-94

issue

eissn

1007-9327

issn

2219-2840

journal_volume

pub_type

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JNKs, insulin resistance and inflammation: A possible link between NAFLD and coronary artery disease.