Immunometabolism of AMPK in insulin resistance and atherosclerosis

Mol Cell Endocrinol. 2013 Feb 25;366(2):224-34. doi: 10.1016/j.mce.2012.02.004. Epub 2012 Feb 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Atherosclerosis / etiology
  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism*
  • Atherosclerosis / physiopathology
  • Cytokines / immunology
  • Cytokines / pharmacology
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Energy Metabolism / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / etiology
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Insulin Resistance*
  • Lipid Peroxidation / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Obesity / complications
  • Obesity / immunology
  • Obesity / metabolism*
  • Obesity / physiopathology
  • Signal Transduction / drug effects

Substances

  • Cytokines
  • AMP-Activated Protein Kinases