title: Notch signaling and M1 macrophage activation in obesity-alcohol synergism.
abstract: Macrophages are a key cell type in the innate immune system, and its proinflammatory (M1) activation in the liver plays a critical role in pathogenesis of alcoholic steatohepatitis. Emerging evidence indicates the involvement of Notch signaling in regulation of innate immune response and cellular metabolism. Metabolic switch to glycolysis characterizes macrophages undergoing M1 activation. It has been proposed that metabolic reprograming in response to extrinsic stimulation, such as bacterial endotoxin, triggers intrinsic signal to dictate cell differentiation. Using an obesity-alcohol synergistic ASH mouse model, we have recently shown that Notch1 pathway promotes M1 activation of hepatic macrophages, through direct upregulation of M1 gene transcription and through reprograming of mitochondrial metabolism to glucose oxidation and subsequent mtROS generation to augment M1 gene expression. Our studies demonstrate a novel mechanism of Notch1 signaling in metabolic reprograming of macrophage for M1 activation in ASH.
authors.affiliation: Department of Pathology, Southern California Research Center for ALPD and Cirrhosis, the Keck School of Medicine, University of Southern California, Los Angeles, USA. Electronic address: junx@usc.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pathology, Southern California Research Center for ALPD and Cirrhosis, the Keck School of Medicine, University of Southern California, Los Angeles, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Chi
authors.affiliation: Department of Pathology, Southern California Research Center for ALPD and Cirrhosis, the Keck School of Medicine, University of Southern California, Los Angeles, USA.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tsukamoto
mesh_terms: D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005234:Fatty Liver / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D009765:Obesity / Q000150:complications*; D017382:Reactive Oxygen Species; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D051880:Receptors, Notch; D000431:Ethanol; D005947:Glucose