Metabolic Remodeling in Fontan Patients

2019 ◽  
Author(s):  
Keyword(s):  
Metabolic Remodeling ◽  
Fontan Patients

Impact of the Fontan Operation on Organ Systems

2019 ◽  
Vol 19 (3) ◽  
pp. 205-214
Author(s):  
Miriam Michel ◽  
Manuela Zlamy ◽  
Andreas Entenmann ◽  
Karin Pichler ◽  
Sabine Scholl-Bürgi ◽  
...  
Keyword(s):  
Systematic Study ◽  
Fontan Operation ◽  
Gastrointestinal System ◽  
Adjunct Treatment ◽  
Organ Systems ◽  
Fontan Surgery ◽  
Fontan Patients

: In patients having undergone the Fontan operation, besides the well discussed changes in the cardiac, pulmonary and gastrointestinal system, alterations of further organ systems including the hematologic, immunologic, endocrinological and metabolic are reported. As a medical adjunct to Fontan surgery, the systematic study of the central role of the liver as a metabolizing and synthesizing organ should allow for a better understanding of the pathomechanism underlying the typical problems in Fontan patients, and in this context, the profiling of endocrinological and metabolic patterns might offer a tool for the optimization of Fontan follow-up, targeted monitoring and specific adjunct treatment.

scholarly journals Muscle unloading-induced metabolic remodeling is associated with acute alterations in PPARδ and UCP-3 expression

2008 ◽  
Vol 34 (2) ◽  
pp. 149-161 ◽  
Author(s):  
Dawn J. Mazzatti ◽  
Melissa A. Smith ◽  
Radu C. Oita ◽  
Fei-Ling Lim ◽  
Andrew J. White ◽  
...  
Keyword(s):  
Differential Expression ◽  
Fiber Type ◽  
Uncoupling Protein ◽  
Hindlimb Suspension ◽  
Metabolic Flexibility ◽  
Peroxisome Proliferator ◽  
Compensatory Response ◽  
Mouse Muscle ◽  
Metabolic Remodeling ◽  
Muscle Unloading

A number of physiological changes follow prolonged skeletal muscle unloading as occurs in spaceflight, bed rest, and hindlimb suspension (HLS) and also in aging. These include muscle atrophy, fiber type switching, and loss of the ability to switch between lipid and glucose usage, or metabolic inflexibility. The signaling and genomic events that precede these physiological manifestations have not been investigated in detail, particularly in regard to loss of metabolic flexibility. Here we used gene arrays to determine the effects of 24-h HLS on metabolic remodeling in mouse muscle. Acute unloading resulted in differential expression of a number of transcripts in soleus and gastrocnemius muscle, including many involved in lipid and glucose metabolism. These include the peroxisome proliferator-activated receptors (PPARs). In contrast to Ppar-α and Ppar-γ, which were downregulated by acute HLS, Ppar-δ was upregulated concomitant with increased expression of its downstream target, uncoupling protein-3 ( Ucp-3). However, differential expression of Ppar-δ was both acute and transient in nature, suggesting that regulation of PPARδ may represent an adaptive, compensatory response aimed at regulating fuel utilization and maintaining metabolic flexibility.

scholarly journals Metabolic remodeling of dystrophic skeletal muscle reveals biological roles for dystrophin and utrophin in adaptation and plasticity

2020 ◽  
pp. 101157
Author(s):  
Justin P. Hardee ◽  
Karen J.B. Martins ◽  
Paula M. Miotto ◽  
James G. Ryall ◽  
Stefan M. Gehrig ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Remodeling

scholarly journals Induction and Increased Risk of Infections in Pediatric Fontan Patients after Heart Transplantation

2021 ◽  
Vol 40 (4) ◽  
pp. S120
Author(s):  
H. Ahmed ◽  
J. Lee ◽  
D. Bernstein ◽  
K. Weinberg ◽  
D.N. Rosenthal ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Increased Risk ◽  
Fontan Patients

scholarly journals Embryonic Origin and Subclonal Evolution of Tumor-Associated Macrophages Imply Preventive Care for Cancer

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 903
Author(s):  
Xiao-Mei Zhang ◽  
De-Gao Chen ◽  
Shengwen Calvin Li ◽  
Bo Zhu ◽  
Zhong-Jun Li
Keyword(s):  
Metabolic Regulation ◽  
Transcriptional Profiling ◽  
Tumor Development ◽  
Metabolic Reprogramming ◽  
Cancer Therapies ◽  
Functional Heterogeneity ◽  
Tumor Associated Macrophages ◽  
Metabolic Remodeling ◽  
And Function ◽  
Mapping Models

Macrophages are widely distributed in tissues and function in homeostasis. During cancer development, tumor-associated macrophages (TAMs) dominatingly support disease progression and resistance to therapy by promoting tumor proliferation, angiogenesis, metastasis, and immunosuppression, thereby making TAMs a target for tumor immunotherapy. Here, we started with evidence that TAMs are highly plastic and heterogeneous in phenotype and function in response to microenvironmental cues. We pointed out that efforts to tear off the heterogeneous “camouflage” in TAMs conduce to target de facto protumoral TAMs efficiently. In particular, several fate-mapping models suggest that most tissue-resident macrophages (TRMs) are generated from embryonic progenitors, and new paradigms uncover the ontogeny of TAMs. First, TAMs from embryonic modeling of TRMs and circulating monocytes have distinct transcriptional profiling and function, suggesting that the ontogeny of TAMs is responsible for the functional heterogeneity of TAMs, in addition to microenvironmental cues. Second, metabolic remodeling helps determine the mechanism of phenotypic and functional characteristics in TAMs, including metabolic bias from macrophages’ ontogeny in macrophages’ functional plasticity under physiological and pathological conditions. Both models aim at dissecting the ontogeny-related metabolic regulation in the phenotypic and functional heterogeneity in TAMs. We argue that gleaning from the single-cell transcriptomics on subclonal TAMs’ origins may help understand the classification of TAMs’ population in subclonal evolution and their distinct roles in tumor development. We envision that TAM-subclone-specific metabolic reprogramming may round-up with future cancer therapies.

scholarly journals Revealing the Metabolic Alterations during Biofilm Development of Burkholderia cenocepacia Based on Genome-Scale Metabolic Modeling

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 221
Author(s):  
Ozlem Altay ◽  
Cheng Zhang ◽  
Hasan Turkez ◽  
Jens Nielsen ◽  
Mathias Uhlén ◽  
...  
Keyword(s):  
Systems Biology ◽  
Alternative Pathway ◽  
Growth Conditions ◽  
Pentose Phosphate ◽  
Burkholderia Cenocepacia ◽  
Bacterial Cells ◽  
Metabolic Remodeling ◽  
Transcriptomics Data ◽  
Biofilm Development ◽  
Genome Scale

Burkholderia cenocepacia is among the important pathogens isolated from cystic fibrosis (CF) patients. It has attracted considerable attention because of its capacity to evade host immune defenses during chronic infection. Advances in systems biology methodologies have led to the emergence of methods that integrate experimental transcriptomics data and genome-scale metabolic models (GEMs). Here, we integrated transcriptomics data of bacterial cells grown on exponential and biofilm conditions into a manually curated GEM of B. cenocepacia. We observed substantial differences in pathway response to different growth conditions and alternative pathway susceptibility to extracellular nutrient availability. For instance, we found that blockage of the reactions was vital through the lipid biosynthesis pathways in the exponential phase and the absence of microenvironmental lysine and tryptophan are essential for survival. During biofilm development, bacteria mostly had conserved lipid metabolism but altered pathway activities associated with several amino acids and pentose phosphate pathways. Furthermore, conversion of serine to pyruvate and 2,5-dioxopentanoate synthesis are also identified as potential targets for metabolic remodeling during biofilm development. Altogether, our integrative systems biology analysis revealed the interactions between the bacteria and its microenvironment and enabled the discovery of antimicrobial targets for biofilm-related diseases.

scholarly journals Myocardial Deformation in Fontan Patients Assessed by Cardiac Magnetic Resonance Feature Tracking: Correlation with Function, Clinical Course, and Biomarkers

2021 ◽  
Author(s):  
Alessia Callegari ◽  
Simona Marcora ◽  
Barbara Burkhardt ◽  
Michael Voutat ◽  
Christian Johannes Kellenberger ◽  
...  
Keyword(s):  
Ventricular Function ◽  
Feature Tracking ◽  
Heart Diseases ◽  
Fontan Operation ◽  
Myocardial Deformation ◽  
Time Interval ◽  
Ventricular Volumes ◽  
Atrioventricular Valve Regurgitation ◽  
Cine Mr ◽  
Fontan Patients

AbstractCardiac MR (CMR) is a standard modality for assessing ventricular function of single ventricles. CMR feature-tracking (CMR-FT) is a novel application enabling strain measurement on cine MR images and is used in patients with congenital heart diseases. We sought to assess the feasibility of CMR-FT in Fontan patients and analyze the correlation between CMR-FT strain values and conventional CMR volumetric parameters, clinical findings, and biomarkers. Global circumferential (GCS) and longitudinal (GLS) strain were retrospectively measured by CMR-FT on Steady-State Free Precession cine images. Data regarding post-operative course at Fontan operation, and medication, exercise capacity, invasive hemodynamics, and blood biomarkers at a time interval ± 6 months from CMR were collected. Forty-seven patients underwent CMR 11 ± 6 years after the Fontan operation; age at CMR was 15 ± 7 years. End-diastolic volume (EDV) of the SV was 93 ± 37 ml/m2, end-systolic volume (ESV) was 46 ± 23 ml/m2, and ejection fraction (EF) was 51 ± 11%. Twenty (42%) patients had a single right ventricle (SRV). In single left ventricle (SLV), GCS was higher (p < 0.001), but GLS was lower (p = 0.04) than in SRV. GCS correlated positively with EDV (p = 0.005), ESV (p < 0.001), and EF (p ≤ 0.0001). GLS correlated positively with EF (p = 0.002), but not with ventricular volumes. Impaired GCS correlated with decreased ventricular function (p = 0.03) and atrioventricular valve regurgitation (p = 0.04) at echocardiography, direct atriopulmonary connection (p = 0.02), post-operative complications (p = 0.05), and presence of a rudimentary ventricle (p = 0.01). A reduced GCS was associated with increased NT-pro-BNP (p = 0.05). Myocardial deformation can be measured by CMR-FT in Fontan patients. SLVs have higher GCS, but lower GLS than SRVs. GCS correlates with ventricular volumes and EF, whereas GLS correlates with EF only. Myocardial deformation shows a relationship with several clinical parameters and NT-pro-BNP.

scholarly journals Changes in retinoid metabolism and signaling associated with metabolic remodeling during fasting and in type I diabetes.

2021 ◽  
pp. 100323
Author(s):  
Alla V. Klyuyeva ◽  
Olga V. Belyaeva ◽  
Kelli R. Goggans ◽  
Wojciech Krezel ◽  
Kirill M. Popov ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Type I ◽  
Retinoid Metabolism ◽  
Metabolic Remodeling

scholarly journals Transcriptomic and Metabolic Network Analysis of Metabolic Reprogramming and IGF-1 Modulation in SCA3 Transgenic Mice

2021 ◽  
Vol 22 (15) ◽  
pp. 7974
Author(s):  
Yu-Te Lin ◽  
Yong-Shiou Lin ◽  
Wen-Ling Cheng ◽  
Jui-Chih Chang ◽  
Yi-Chun Chao ◽  
...  
Keyword(s):  
Network Analysis ◽  
Transgenic Mice ◽  
Signaling Pathways ◽  
Metabolic Network ◽  
Metabolic Reprogramming ◽  
Spinocerebellar Ataxia Type ◽  
Positive Effects ◽  
Metabolic Network Analysis ◽  
Potential Biomarker ◽  
Metabolic Remodeling

Spinocerebellar ataxia type 3 (SCA3) is a genetic neurodegenerative disease for which a cure is still needed. Growth hormone (GH) therapy has shown positive effects on the exercise behavior of mice with cerebellar atrophy, retains more Purkinje cells, and exhibits less DNA damage after GH intervention. Insulin-like growth factor 1 (IGF-1) is the downstream mediator of GH that participates in signaling and metabolic regulation for cell growth and modulation pathways, including SCA3-affected pathways. However, the underlying therapeutic mechanisms of GH or IGF-1 in SCA3 are not fully understood. In the present study, tissue-specific genome-scale metabolic network models for SCA3 transgenic mice were proposed based on RNA-seq. An integrative transcriptomic and metabolic network analysis of a SCA3 transgenic mouse model revealed that metabolic signaling pathways were activated to compensate for the metabolic remodeling caused by SCA3 genetic modifications. The effect of IGF-1 intervention on the pathology and balance of SCA3 disease was also explored. IGF-1 has been shown to invoke signaling pathways and improve mitochondrial function and glycolysis pathways to restore cellular functions. As one of the downregulated factors in SCA3 transgenic mice, IGF-1 could be a potential biomarker and therapeutic target.

Sign in / Sign up

Export Citation Format

Share Document