scholarly journals COVID-19 Comorbidity and Metabolic Syndrome: Is There a Molecular Basis?

2020 ◽  
Author(s):  
Madhurima Basu ◽  
Chinmay Saha ◽  
Kamalika Roy Choudhury ◽  
Susmita Dutta ◽  
Sujoy Ghosh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Molecular Basis ◽  
Metabolic Diseases ◽  
Viral Proteins ◽  
Host Protein ◽  
Acid Oxidation ◽  
Biological Processes ◽  
Host Proteins ◽  
Alcoholic Fatty Liver

The risk factors associated with COVID-19 related severity, morbidity, and mortality, i.e., obesity (often associated with NAFLD), hyperglycemia, hypertension and dyslipidemia all cluster together as metabolic syndrome (MetS). Instead of studying association of these risk factors with COVID-19, it makes sense studying the association between MetS on one hand and COVID-19 on the other. This study explores a molecular basis underpinning the above association. Severity of COVID-19 patients with MetS could be due to functional alterations of host proteins due to their interactions with viral proteins. We collected data from Enrichr (https://amp.pharm.mssm.edu/Enrichr/), DisGeNET (https://www.disgenet.org/) and others and carried out enrichment analysis using Enrichr. Various biological processes and pathways associated with viral protein interacting partners are known to involve in metabolic diseases. The molecular pathways underlying insulin resistance, insulin signaling and insulin secretion are not only involved in diabetes but also in CVD and obesity (associated with non-alcoholic fatty liver disease; NAFLD). Lipid metabolism/lipogenesis, fatty acid oxidation and inflammation are associated with MetS. Viral interacting host proteins are associated and enriched with terms like hyperglycemia, coronary artery disease, hypertensive disease related to CVD and liver diseases in DisGeNET. Association of viral interacting proteins with disease-relevant biological processes, pathways and disease-related terms suggests that altered host protein function following interaction with viral proteins might contribute to frequent occurrence and/or severity of COVID-19 in subjects with MetS. Such analysis not only provides a molecular basis of comorbidity but also incriminates host proteins in viral replication, growth and identifies possible drug targets for intervention.

scholarly journals Peroxisome Proliferator-Activated Receptor Targets for the Treatment of Metabolic Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Francisco A. Monsalve ◽  
Radha D. Pyarasani ◽  
Fernando Delgado-Lopez ◽  
Rodrigo Moore-Carrasco
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Glucose Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Atherogenic Dyslipidemia ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
The Metabolic Syndrome

Metabolic syndrome is estimated to affect more than one in five adults, and its prevalence is growing in the adult and pediatric populations. The most widely recognized metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a proinflammatory state as well. Peroxisome proliferator-activated receptors (PPARs) may serve as potential therapeutic targets for treating the metabolic syndrome and its related risk factors. The PPARs are transcriptional factors belonging to the ligand-activated nuclear receptor superfamily. So far, three isoforms of PPARs have been identified, namely, PPAR-α, PPAR-β/δ, and PPAR-γ. Various endogenous and exogenous ligands of PPARs have been identified. PPAR-αand PPAR-γare mainly involved in regulating lipid metabolism, insulin sensitivity, and glucose homeostasis, and their agonists are used in the treatment of hyperlipidemia and T2DM. Whereas PPAR-β/δfunction is to regulate lipid metabolism, glucose homeostasis, anti-inflammation, and fatty acid oxidation and its agonists are used in the treatment of metabolic syndrome and cardiovascular diseases. This review mainly focuses on the biological role of PPARs in gene regulation and metabolic diseases, with particular focus on the therapeutic potential of PPAR modulators in the treatment of thrombosis.

scholarly journals Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Antonino Mulè ◽  
Eleonora Bruno ◽  
Patrizia Pasanisi ◽  
Letizia Galasso ◽  
Lucia Castelli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Circadian Rhythm ◽  
Metabolic Diseases ◽  
Activity Level ◽  
Activity Count ◽  
Cross Sectional ◽  
The Metabolic Syndrome ◽  
Parametric Analyses ◽  
Rest Activity

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person’s circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.

scholarly journals Molecular Basis of the Ternary Interaction between NS1 of the 1918 Influenza A Virus, PI3K, and CRK

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 338
Author(s):  
Alyssa Dubrow ◽  
Sirong Lin ◽  
Nowlan Savage ◽  
Qingliang Shen ◽  
Jae-Hyun Cho
Keyword(s):  
Influenza A Virus ◽  
Molecular Basis ◽  
Influenza A ◽  
Host Protein ◽  
Structural Protein ◽  
Host Proteins ◽  
Ternary Interaction ◽  
Important Virulence Factor ◽  
1918 Influenza ◽  
Phosphoinositide 3 Kinase

The 1918 influenza A virus (IAV) caused the worst flu pandemic in human history. Non-structural protein 1 (NS1) is an important virulence factor of the 1918 IAV and antagonizes host antiviral immune responses. NS1 increases virulence by activating phosphoinositide 3-kinase (PI3K) via binding to the p85β subunit of PI3K. Intriguingly, unlike the NS1 of other human IAV strains, 1918 NS1 hijacks another host protein, CRK, to form a ternary complex with p85β, resulting in hyperactivation of PI3K. However, the molecular basis of the ternary interaction between 1918 NS1, CRK, and PI3K remains elusive. Here, we report the structural and thermodynamic bases of the ternary interaction. We find that the C-terminal tail (CTT) of 1918 NS1 remains highly flexible in the complex with p85β. Thus, the CTT of 1918 NS1 in the complex with PI3K can efficiently hijack CRK. Notably, our study indicates that 1918 NS1 enhances its affinity to p85β in the presence of CRK, which might result in enhanced activation of PI3K. Our results provide structural insight into how 1918 NS1 hijacks two host proteins simultaneously.

scholarly journals Aerobic interval training improves irisin and chemerin levels of both liver and visceral adipose tissues and circulating asprosin in rats with metabolic syndrome

2021 ◽  
Author(s):  
Fereshteh Ahmadabadi ◽  
Hossein Nakhaei ◽  
Mehdi Mogharnasi ◽  
Chun-Jung Huang
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Cardiometabolic Risk ◽  
Exercise Intervention ◽  
Metabolic Diseases ◽  
Interval Training ◽  
Cardiometabolic Risk Factors ◽  
Continuous Training ◽  
Aerobic Interval Training ◽  
Visceral Adipose

Abstract The perturbation of adipokinetic hormones, such as irisin, chemerin, and asprosin has been reported to participate in pathological conditions (e.g., insulin resistance) and chronic inflammation. However, exercise training has been long established as an effective intervention for prevention and treatment of these chronic and metabolic diseases. This study was to examine the effects of aerobic continuous training (ACT) and aerobic interval training (AIT) on irisin and chemerin levels of liver tissue (LT) and visceral adipose tissue (VAT), circulating asprosin, and their relationships with cardiometabolic risk factors in rats with metabolic syndrome (MetS). Thirty-two male Wistar rats were randomly divided into four equal groups: normal control (N-Ctr), control (Ctr-MetS), ACT, and AIT. After familiarization, rats with exercise intervention performed either ACT or AIT five times a week over eight weeks. The level of irisin in both ACT and AIT groups was higher than the Ctr-MetS group in LT and VAT, with a greater improvement of LT level observed in AIT vs. ACT groups. Furthermore, the level of chemerin in LT and VAT was lower in both ACT and AIT groups than the Ctr-MetS group, whereas only AIT group exhibited a reduction of serum asprosin when compared to ACT and Ctr-MetS, along with the improvements of cardiometabolic markers, such as HOMA-IR and lipid profile. These findings may support the efficiency and effectiveness of AIT intervention in the modulation of these novel metabolic hormones and cardiometabolic risk factors for reduced risk of metabolic syndrome.

scholarly journals Network-Guided Discovery of Influenza Virus Replication Host Factors

2018 ◽  
Author(s):  
Emily E. Ackerman ◽  
Eiryo Kawakami ◽  
Manami Katoh ◽  
Tokiko Watanabe ◽  
Shinji Watanabe ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Replication ◽  
Drug Targets ◽  
Antiviral Drug ◽  
Viral Proteins ◽  
Host Factors ◽  
Host Protein ◽  
Ppi Network ◽  
Host Proteins ◽  
Influenza Virus Replication

ABSTRACTThe position of host factors required for viral replication within a human protein-protein interaction (PPI) network can be exploited to identify drug targets that are robust to drug-mediated selective pressure. Host factors can physically interact with viral proteins, be a component of pathways regulated by viruses (where proteins themselves do not interact with viral proteins) or be required for viral replication but unregulated by viruses. Here, we demonstrate a method of combining a human PPI network with virus-host protein interaction data to improve antiviral drug discovery for influenza viruses by identifying target host proteins. Network analysis shows that influenza virus proteins physically interact with host proteins in network positions significant for information flow. We have isolated a subnetwork of the human PPI network which connects virus-interacting host proteins to host factors that are important for influenza virus replication without physically interacting with viral proteins. The subnetwork is enriched for signaling and immune processes. Selecting proteins based on network topology within the subnetwork, we performed an siRNA screen to determine if the subnetwork was enriched for virus replication host factors and if network position within the subnetwork offers an advantage in prioritization of drug targets to control influenza virus replication. We found that the subnetwork is highly enriched for target host proteins – more so than the set of host factors that physically interact with viral proteins. Our findings demonstrate that network positions are a powerful predictor to guide antiviral drug candidate prioritization.IMPORTANCEIntegrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e. proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates.

scholarly journals Impact Analysis of SARS-CoV2 on Signaling Pathways during COVID19 Pathogenesis using Codon Usage Assisted Host-Viral Protein Interactions

2020 ◽  
Author(s):  
Jayanta Kumar Das ◽  
Subhadip Chakraborty ◽  
Swarup Roy
Keyword(s):  
Codon Usage ◽  
Signaling Pathways ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Viral Protein ◽  
Viral Proteins ◽  
Host Protein ◽  
Host Proteins ◽  
Disease Pathogenesis ◽  
Pattern Similarity

AbstractUnderstanding the molecular mechanism of COVID19 disease pathogenesis helps in the rapid development of therapeutic targets. Usually, viral protein targets host proteins in an organized fashion. The pathogen may target cell signaling pathways to disrupt the pathway genes’ regular activities, resulting in disease. Understanding the interaction mechanism of viral and host proteins involved in different signaling pathways may help decipher the attacking mechanism on the signal transmission during diseases, followed by discovering appropriate therapeutic solutions.The expression of any viral gene depends mostly on the host translational machinery. Recent studies report the great significance of codon usage biases in establishing host-viral protein-protein interactions (PPI). Exploiting the codon usage patterns between a pair of co-evolved host and viral proteins may present novel insight into the host-viral protein interactomes during disease pathogenesis. Leveraging the codon usage pattern similarity (and dissimilarity), we propose a computational scheme to recreate the hostviral protein interaction network (HVPPI). We use seventeen (17) essential signaling pathways for our current work and study the possible targeting mechanism of SARS-CoV2 viral proteins on such pathway proteins. We infer both negatively and positively interacting edges in the network. We can find a relationship where one host protein may target by more than one viral protein.Extensive analysis performed to understand the network topologically and the attacking behavior of the viral proteins. Our study reveals that viral proteins, mostly utilize codons, rare in the targeted host proteins (negatively correlated interaction). Among non-structural proteins, NSP3 and structural protein, Spike (S) protein, are the most influential proteins in interacting multiple host proteins. In ranking the most affected pathways, MAPK pathways observe to be worst affected during the COVID-19 disease. A good number of targeted proteins are highly central in host protein interaction networks. Proteins participating in multiple pathways are also highly connected in their own PPI and mostly targeted by multiple viral proteins.

scholarly journals Metabolic syndrome and risk factors for non-alcoholic fatty liver disease

2012 ◽  
Vol 49 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Mônica Rodrigues de Araújo Souza ◽  
Margareth de Fátima Formiga de Melo Diniz ◽  
José Eymard Moraes de Medeiros-Filho ◽  
Maria Salete Trigueiro de Araújo
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Experimental Studies ◽  
Final Analysis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

CONTEXT: Non-alcoholic fatty liver disease (NAFLD), hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS) to non-alcoholic steatohepatitis (NASH). The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1) recognize patients with metabolic syndrome at high risk for NAFLD, 2) elucidate pathways common to other co-morbidities, 3) determine risk factors associated with a worse prognosis, 4) develop therapeutic strategies with goal of reducing risk factors, 5) apply acquired knowledge in public health policies focusing on preventive strategies.

MicroRNA regulation of mitochondrial and ER stress signaling pathways: implications for lipoprotein metabolism in metabolic syndrome

2014 ◽  
Vol 307 (9) ◽  
pp. E729-E737 ◽  
Author(s):  
Patricia Christian ◽  
Qiaozhu Su
Keyword(s):  
Metabolic Syndrome ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Acid Oxidation ◽  
Aberrant Expression ◽  
The Metabolic Syndrome ◽  
Mitochondrial Fatty Acid

The development of metabolic syndrome is closely associated with the deregulation of lipid metabolism. Emerging evidence has demonstrated that microRNAs (miRNAs) are intensively engaged in lipid and lipoprotein metabolism by regulating genes involved in control of intracellular lipid synthesis, mitochondrial fatty acid oxidation, and lipoprotein assembly. Mitochondrial dysfunction induced by altered miRNA expression has been proposed to be a contributing factor in the onset of metabolic diseases, while at the same time, aberrant expression of certain miRNAs is associated with the induction of endoplasmic reticulum (ER) stress induced by nutrient-surplus. These studies position miRNAs as a link between oxidative stress and ER stress, two cellular stress pathways that are deregulated in metabolic disease and are associated with very-low-density lipoprotein (VLDL) overproduction. Dyslipoproteinemia frequently accompanied with metabolic syndrome is initiated largely by the overproduction of VLDL and altered biogenesis of high-density lipoprotein (HDL). In this review, we highlight recent findings on the regulatory impact of miRNAs on the metabolic homeostasis of mitochondria and ER as well as their contribution to the aberrant biogenesis of both VLDL and HDL in the context of metabolic disorders, in an attempt to gain further insights into the molecular mechanisms of dyslipidemia in the metabolic syndrome.

scholarly journals Association of Cardiovascular Risk Factors and Metabolic Syndrome with non-alcoholic and alcoholic fatty liver disease: a retrospective analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. L. Han
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Cardiovascular Risk ◽  
Liver Disease ◽  
Fatty Liver ◽  
Cardiovascular Risk Factors ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Healthy Group ◽  
Alcoholic Fatty Liver Disease

Abstract Background Although many studies on non-alcoholic fatty liver disease (NAFLD) are underway worldwide, and several existing studies have investigated the association between NAFLD and cardiovascular risk factors, studies comparing NAFLD and alcoholic fatty liver disease (AFLD) are scarce. This study aimed to evaluate differences between the incidence of cardiovascular risk factors and metabolic syndrome in NAFLD and AFLD. Methods A retrospective analysis of 913 patients who underwent abdominal computed tomography (CT) was performed to compare the incidence of cardiovascular risk factors and metabolic syndrome between NAFLD and AFLD. Subjects were divided into three groups based on criteria: healthy (n = 572), NAFLD (n = 295), and AFLD (n = 46). The healthy group had no liver disease. NAFLD was defined as fatty liver diagnosed on CT and drinking less than 140 g/week for men or 70 g/week for women. AFLD was defined as fatty liver diagnosed on CT and drinking more than 140 g/week for men or 70 g/week for women. We compared the incidence of cardiovascular risk factors and metabolic syndrome between the three groups. The relationship between each group and the metabolic syndrome risk was analyzed through multivariate logistic regression analysis. Results No significant differences in several cardiovascular risk factors were observed between the NAFLD and AFLD groups. Upon analyzing the metabolic syndrome status in each group after making appropriate adjustments, the odds ratios (ORs) in the NAFLD (OR = 2.397, P = 0.002) and AFLD groups (OR = 4.445, P = 0.001) were found to be significantly higher than that in the healthy group; the incidence rate of metabolic syndrome was similar in the NAFLD and AFLD groups. Conclusions Both the NAFLD and AFLD groups had more cardiovascular risk factors and higher metabolic syndrome risk than the healthy group. Thus, the prevention of fatty liver disease, regardless of the specific type, should involve the identification of cardiovascular and metabolic syndrome risk factors. If abdominal CT reveals a fatty liver, whether NAFLD or AFLD, the risk of cardiovascular disease and metabolic syndrome should be assessed.

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