scholarly journals A Metabolic Switching Hypothesis for the First Step in the Hypolipidemic Effects of Fibrates

2002 ◽  
Vol 25 (11) ◽  
pp. 1509-1511 ◽  
Author(s):  
Kiyoto Motojima
Keyword(s):  
Metabolic Switching

scholarly journals Metabolic Switching of Mycobacterium tuberculosis during Hypoxia Is Controlled by the Virulence Regulator PhoP

2020 ◽  
Vol 202 (7) ◽  
Author(s):  
Prabhat Ranjan Singh ◽  
Anil Kumar Vijjamarri ◽  
Dibyendu Sarkar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nitrogen Metabolism ◽  
Electron Acceptor ◽  
Latent Infection ◽  
Critical Role ◽  
Hypoxic Stress ◽  
Content Type ◽  
Metabolic Switching ◽  
Virulence Regulator

ABSTRACT Mycobacterium tuberculosis retains the ability to establish an asymptomatic latent infection. A fundamental question in mycobacterial physiology is to understand the mechanisms involved in hypoxic stress, a critical player in persistence. Here, we show that the virulence regulator PhoP responds to hypoxia, the dormancy signal, and effectively integrates hypoxia with nitrogen metabolism. We also provide evidence to demonstrate that both under nitrogen limiting conditions and during hypoxia, phoP locus controls key genes involved in nitrogen metabolism. Consistently, under hypoxia a ΔphoP strain shows growth attenuation even with surplus nitrogen, the alternate electron acceptor, and complementation of the mutant restores bacterial growth. Together, our observations provide new biological insights into the role of PhoP in integrating nitrogen metabolism with hypoxia by the assistance of the hypoxia regulator DosR. The results have significant implications on the mechanism of intracellular survival and growth of the tubercle bacilli under a hypoxic environment within the phagosome. IMPORTANCE M. tuberculosis retains the unique ability to establish an asymptomatic latent infection. To understand the mechanisms involved in hypoxic stress which play a critical role in persistence, we show that the virulence regulator PhoP is linked to hypoxia, the dormancy signal. In keeping with this, phoP was shown to play a major role in M. tuberculosis growth under hypoxia even in the presence of surplus nitrogen, the alternate electron acceptor. Our results showing regulation of hypoxia-responsive genes provide new biological insights into role of the virulence regulator in metabolic switching by sensing hypoxia and integrating nitrogen metabolism with hypoxia by the assistance of the hypoxia regulator DosR.

scholarly journals Spatiotemporal gating of SIRT1 functions by O-GlcNAcylation is essential for liver metabolic switching and prevents hyperglycemia

2020 ◽  
Vol 117 (12) ◽  
pp. 6890-6900 ◽  
Author(s):  
Tandrika Chattopadhyay ◽  
Babukrishna Maniyadath ◽  
Hema P. Bagul ◽  
Arindam Chakraborty ◽  
Namrata Shukla ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Nutrient Inputs ◽  
Fed State ◽  
Physiological Fitness ◽  
Metabolic Switching ◽  
Nuclear Exclusion ◽  
Aberrant Gene Expression ◽  
Systemic Insulin Resistance ◽  
Aberrant Gene

Inefficient physiological transitions are known to cause metabolic disorders. Therefore, investigating mechanisms that constitute molecular switches in a central metabolic organ like the liver becomes crucial. Specifically, upstream mechanisms that control temporal engagement of transcription factors, which are essential to mediate physiological fed–fast–refed transitions are less understood. SIRT1, a NAD+-dependent deacetylase, is pivotal in regulating hepatic gene expression and has emerged as a key therapeutic target. Despite this, if/how nutrient inputs regulate SIRT1 interactions, stability, and therefore downstream functions are still unknown. Here, we establish nutrient-dependent O-GlcNAcylation of SIRT1, within its N-terminal domain, as a crucial determinant of hepatic functions. Our findings demonstrate that during a fasted-to-refed transition, glycosylation of SIRT1 modulates its interactions with various transcription factors and a nodal cytosolic kinase involved in insulin signaling. Moreover, sustained glycosylation in the fed state causes nuclear exclusion and cytosolic ubiquitin-mediated degradation of SIRT1. This mechanism exerts spatiotemporal control over SIRT1 functions by constituting a previously unknown molecular relay. Of note, loss of SIRT1 glycosylation discomposed these interactions resulting in aberrant gene expression, mitochondrial dysfunctions, and enhanced hepatic gluconeogenesis. Expression of nonglycosylatable SIRT1 in the liver abrogated metabolic flexibility, resulting in systemic insulin resistance, hyperglycemia, and hepatic inflammation, highlighting the physiological costs associated with its overactivation. Conversely, our study also reveals that hyperglycosylation of SIRT1 is associated with aging and high-fat–induced obesity. Thus, we establish that nutrient-dependent glycosylation of SIRT1 is essential to gate its functions and maintain physiological fitness.

scholarly journals Publisher Correction: Intermittent metabolic switching, neuroplasticity and brain health

2020 ◽  
Vol 21 (8) ◽  
pp. 445-445
Author(s):  
Mark P. Mattson ◽  
Keelin Moehl ◽  
Nathaniel Ghena ◽  
Maggie Schmaedick ◽  
Aiwu Cheng
Keyword(s):  
Brain Health ◽  
Metabolic Switching

scholarly journals Novel roles of immunometabolism and nonmyocyte metabolism in cardiac remodeling and injury

2020 ◽  
Vol 319 (4) ◽  
pp. R476-R484
Author(s):  
Alan J. Mouton ◽  
John E. Hall
Keyword(s):  
Endothelial Cells ◽  
Cardiac Remodeling ◽  
Immune Cell ◽  
Cardiac Fibroblasts ◽  
Cardiac Injury ◽  
Phenotypic Switching ◽  
Glycolytic Metabolism ◽  
Cell Dysfunction ◽  
Metabolic Switching ◽  
Review Current

Changes in cardiomyocyte metabolism have been heavily implicated in cardiac injury and heart failure (HF). However, there is emerging evidence that metabolism in nonmyocyte populations, including cardiac fibroblasts, immune cells, and endothelial cells, plays an important role in cardiac remodeling and adaptation to injury. Here, we discuss recent advances and insights into nonmyocyte metabolism in the healthy and injured heart. Metabolic switching from mitochondrial oxidative phosphorylation to glycolysis is critical for immune cell (macrophage and T lymphocyte) and fibroblast phenotypic switching in the inflamed and fibrotic heart. On the other hand, cardiac endothelial cells are heavily reliant on glycolytic metabolism, and thus impairments in glycolytic metabolism underlie endothelial cell dysfunction. Finally, we review current and ongoing metabolic therapies for HF and the potential implications for nonmyocyte metabolism.

Metabolic Switching Provides a Dynamic View of Cellular Bioenergetic Capacity and Flexibility

2013 ◽  
Vol 65 ◽  
pp. S18
Author(s):  
Brian P. Dranka ◽  
Lisa Pike ◽  
Ajit S. Divakaruni ◽  
George W. Rogers ◽  
David A. Ferrick
Keyword(s):  
Metabolic Switching ◽  
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