Nabeebaccus 2017 JCI Insight

From Bioblast
Jump to: navigation, search
Publications in the MiPMap
Nabeebaccus AA, Zoccarato A, Hafstad AD, Santos CX, Aasum E, Brewer AC, Zhang M, Beretta M, Yin X, West JA, Schröder K, Griffin JL, Eykyn TR, Abel ED, Mayr M, Shah AM (2017) Nox4 reprograms cardiac substrate metabolism via protein O-GlcNAcylation to enhance stress adaptation. JCI Insight 2:96184.

» PMID: 29263294 Open Access

Nabeebaccus AA, Zoccarato A, Hafstad AD, Santos CX, Aasum E, Brewer AC, Zhang M, Beretta M, Yin X, West JA, Schröder K, Griffin JL, Eykyn TR, Abel ED, Mayr M, Shah AM (2017) JCI Insight

Abstract: Cardiac hypertrophic remodeling during chronic hemodynamic stress is associated with a switch in preferred energy substrate from fatty acids to glucose, usually considered to be energetically favorable. The mechanistic interrelationship between altered energy metabolism, remodeling, and function remains unclear. The ROS-generating NADPH oxidase-4 (Nox4) is upregulated in the overloaded heart, where it ameliorates adverse remodeling. Here, we show that Nox4 redirects glucose metabolism away from oxidation but increases fatty acid oxidation, thereby maintaining cardiac energetics during acute or chronic stresses. The changes in glucose and fatty acid metabolism are interlinked via a Nox4-ATF4-dependent increase in the hexosamine biosynthetic pathway, which mediates the attachment of O-linked N-acetylglucosamine (O-GlcNAcylation) to the fatty acid transporter CD36 and enhances fatty acid utilization. These data uncover a potentially novel redox pathway that regulates protein O-GlcNAcylation and reprograms cardiac substrate metabolism to favorably modify adaptation to chronic stress. Our results also suggest that increased fatty acid oxidation in the chronically stressed heart may be beneficial.

Keywords: Cardiology, Cardiovascular disease, Intermediary metabolism, Metabolism, Signal transduction Bioblast editor: Kandolf G O2k-Network Lab: NO Tromsoe Larsen TS


Labels: MiParea: Respiration, Genetic knockout;overexpression 


Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria 


Coupling state: LEAK, ET  Pathway: F, N  HRR: Oxygraph-2k 

Labels, 2018-02