Epigenetic mechanisms of macrophage activation in type 2 diabetes.
The alarming rise of obesity and type 2 diabetes (T2D) has put a tremendous strain on global healthcare systems. Over the past decade extensive research has focused on the role of macrophages as key mediators of inflammation in T2D. The inflammatory environment in the obese adipose tissue and pancreatic β-cell islets creates and perpetuates imbalanced inflammatory macrophage activation. Consequences of this chronic low-grade inflammation include insulin resistance in the adipose tissue and pancreatic β-cell dysfunction. Recently, the emerging field of epigenetics has provided new insights into the pathogenesis of T2D, while also affording potential new opportunities for treatment. In macrophages, epigenetic mechanisms are increasingly being recognized as crucial controllers of their phenotype. Here, we first describe the role of macrophages in T2D. Then we elaborate on epigenetic mechanisms that regulate macrophage activation, thereby focusing on T2D. Next, we highlight how diabetic conditions such as hyperlipidemia and hyperglycemia could induce epigenetic changes that promote an inflammatory macrophage phenotype. In conclusion we discuss possible therapeutic interventions by targeting macrophage epigenetics and speculate on future research directions.
Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: m.ahmed@amc.uva.nl.
Mohamed
M
Ahmed
Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands; Institute for Cardiovascular Prevention (IPEK), Ludwig Maximillian's University, Munich, Germany. Electronic address: m.dewinther@amc.uva.nl.
Menno P J
MPJ
de Winther
Experimental Vascular Biology, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ, Amsterdam, The Netherlands. Electronic address: j.vandenbossche@amc.uva.nl.
Jan
J
Van den Bossche
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000276:immunology*; D044127:Epigenesis, Genetic; D006801:Humans; D006943:Hyperglycemia; D006949:Hyperlipidemias; D007249:Inflammation; D008262:Macrophage Activation / Q000235:genetics*; D008264:Macrophages / Q000502:physiology*; D058990:Molecular Targeted Therapy
Epigenetics; Inflammation; Macrophage activation; Obesity; Type 2 diabetes