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Immunometabolism of AMPK in insulin resistance and atherosclerosis

Author:
Fullerton, Morgan D., Steinberg, Gregory R., Schertzer, Jonathan D.
Source:
Molecular and Cellular Endocrinology 2013 v.366 pp. 224-234
ISSN:
0303-7207
Subject:
AMP-activated protein kinase, atherosclerosis, chronic diseases, energy, homeostasis, immune response, inflammation, insulin resistance, lipid peroxidation, noninsulin-dependent diabetes mellitus, obesity, serine, signal transduction, therapeutics, threonine
Abstract:
Obesity leads to insulin resistance and atherosclerosis, which precede Type 2 diabetes and cardiovascular disease. Immunometabolism addresses how metabolic and inflammatory pathways converge to maintain health and a contemporary problem is determining how obesity-induced inflammation precipitates chronic diseases such as insulin resistance and atherosclerosis. AMP-activated protein kinase (AMPK) is an important serine/threonine kinase well known for regulating metabolic processes and maintaining energy homeostasis. However, both metabolic and immunological AMPK-mediated effects play a role in disease. Pro-inflammatory mediators suppress AMPK activity and hinder lipid oxidation. In addition, AMPK activation curbs inflammation by directly inhibiting pro-inflammatory signaling pathways and limiting the build-up of specific lipid intermediates that elicit immune responses. In the context of obesity and chronic disease, these reciprocal responses involve both immune and metabolic cells. Therefore, the immunometabolism of AMPK-mediated processes and therapeutics should be considered in atherosclerosis and insulin resistance.
Agid:
1046476