title: 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.
authors: Department of Clinical and Experimental Medicine, Federico II University Medical School of Naples, Via Sergio Pansini 580131 Naples, Italy. tarantin@unina.it
authors: Giovanni
authors: G
authors: Tarantino
authors: Armando
authors: A
authors: Caputi
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology*; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases