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1.
World J Virol ; 11(2): 98-103, 2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1791990

ABSTRACT

Several mechanisms may explain how exercise training mechanistically confers protection against coronavirus disease 2019 (COVID-19). Here we propose two new perspectives through which cardiorespiratory fitness may protect against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Physical exercise-activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling induces endothelial nitric oxide (NO) synthase (eNOS), increases NO bio-availability, and inhibits palmitoylation, leading to specific and immediate SARS-CoV-2 protection. AMPK signaling also induces angiotensin 1-7 release and enhances eNOS activation thus further mediating cardio- and reno-protection. Irisin, a myokine released from skeletal muscles during aerobic exercise, also participates in the AMPK/Akt-eNOS/NO pathway, protects mitochondrial functions in endothelial cells, and antagonizes renin angiotensin system proinflammatory action leading to reductions in genes associated with severe COVID-19 outcomes. Collectively, all the above findings point to the fact that increased AMPK and irisin activity through exercise training greatly benefits molecular processes that mediate specific, immediate, and delayed SARS-CoV-2 protection. Maintaining regular physical activity levels is a safe and affordable lifestyle strategy against the current and future pandemics and may also mitigate against obesity and cardiometabolic disease syndemics. Move more because a moving target is harder to kill.

2.
Surg Obes Relat Dis ; 16(12): 1910-1918, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1454528

ABSTRACT

BACKGROUND: Bariatric surgery is well established as a treatment for obesity and associated complications. This procedure improves metabolic homeostasis through changes in energy expenditure. We hypothesized that sleeve gastrectomy (SG) improves metabolic homeostasis by modulating energy expenditure and enhancing thermogenesis through increasing the expression level of meteorin-like protein (METRNL) and fibronectin type III domain-containing protein 5 (FNDC5/Irisin) through uncoupling proteins 1/2/3 (UCP1, UCP2, and UCP3). OBJECTIVES: To study the effect of SG on the levels of proteins involved in thermogenesis process. SETTING: Laboratory rats at Kuwait University. METHODS: Male Sprague-Dawley rats, aged 4 to 5 weeks, were divided into 2 groups, control (n = 11) and diet-induced obesity (DIO) (n = 22). The control group was fed regular rat chow ad libitum, whereas the DIO group was fed cafeteria diet "high-fat/carbohydrate diet" ad libitum. At 21 weeks, rats in the DIO group that weighed 20% more than the control group animals underwent surgery. These rats were randomly subdivided into Sham and SG operation groups. Gene expression was evaluated, and enzyme-linked immunosorbent assays were employed to assess the changes in gene and protein levels in tissue and circulation. RESULTS: The protein expression data revealed an increase in METRNL levels in the muscles and white adipose tissue of SG animals. METRNL level in circulation in SG animals was reduced compared with control and Sham rats. The level of Irisin increased in the muscle of SG animals compared with the control and Sham group animals; however, a decrease in Irisin level was observed in the white adipose tissue and brown adipose tissue of SG animals compared with controls. Gene expression analysis revealed decreased METRNL levels in muscle tissues in the SG group compared with the control group animals. Increased expression of FNDC5 (Irisin), UCP2, and UCP3 in the muscle tissue of SG animals was also observed. Furthermore, the levels of UCP1, UCP2, UCP3, and METRNL in the brown adipose tissue of SG animals were upregulated. No significant alteration in the gene expression of Irisin was observed in brown adipose tissue. CONCLUSIONS: Sleeve gastrectomy induces weight loss through complex mechanisms that may include browning of fat.


Subject(s)
Adipose Tissue, Brown , Obesity , Adipose Tissue/metabolism , Animals , Diet , Fibronectins/genetics , Fibronectins/metabolism , Gastrectomy , Kuwait , Male , Mitochondrial Uncoupling Proteins , Muscles/metabolism , Obesity/genetics , Obesity/surgery , Rats , Rats, Sprague-Dawley
3.
Biomolecules ; 11(10)2021 09 28.
Article in English | MEDLINE | ID: covidwho-1444095

ABSTRACT

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.


Subject(s)
COVID-19/metabolism , alpha-2-HS-Glycoprotein/metabolism , Animals , COVID-19/pathology , Male , Rats , Rats, Wistar , alpha-2-HS-Glycoprotein/deficiency
4.
PeerJ ; 9: e11065, 2021.
Article in English | MEDLINE | ID: covidwho-1261423

ABSTRACT

BACKGROUND: Irisin (a glycosylated protein) is cleaved from fibronectin type III domain-containing protein 5 (FNDC5), which is expressed mainly in animal muscle tissues and has multiple metabolic regulatory activities. However, their roles in controlling myofiber types in skeletal muscle remain unclear. METHODOLOGY: Two different commercial hybridized pigs, LJH (a crossed pig containing Chinese native pig genotypes) and DLY (Duroc × Landrace × Yorkshire) were selected to analyze FNDC5 mRNA expression and the mRNA composition of four adult myosin heavy chain (MyHC) isoforms (IIIaIIxIIb) in the longissimus dorsi (LD) muscle. C2C12 myoblasts were cultured to investigate the effects of FNDC5 on the four MyHCs mRNA expressive levels, using small interfering RNA for depletion and a eukaryotic expression vector carrying FNDC5 for overexpression. ZLN005 (a small molecule activator of FNDC5's upstream control gene PGC1α) or recombinant human irisin protein were also used. RESULTS: In LD muscle, LJH pigs had the higher FNDC5 mRNA level, and MyHC I or IIa proportion than DLY pigs (P <  0.05). For C2C12 cells in vitro, small interfering RNA (si-592) silencing of FNDC5 expression markedly reduced MyHC IIa mRNA levels (P <  0.05), while FNDC5 overexpression significantly increased MyHC IIa mRNA levels (P <  0.05). Exogenous irisin increased the mRNA levels of PGC1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), FNDC5, MyHCI, MyHCIIa, NRF1 (nuclear respiratory factor 1), VEGF (vascular endothelial growth factor), and TFAM (mitochondrial transcription factor A,) (P <  0.05), and the enzyme activities of SDH (succinate dehydrogenase), CK (creatine kinase), and MDH (malate dehydrogenase) in C2C12 myotubes (P <  0.05). These results showed that FNDC5 mRNA expression had a significant association with the characteristics of myofiber types in porcine muscle, and participated in regulating MyHCs mRNA expression of C2C12 myogenic differentiation cells in vitro. FNDC5 could be an important factor to control muscle fiber types, which provides a new direction to investigate pork quality via muscle fiber characteristics.

5.
Mol Cell Endocrinol ; 515: 110917, 2020 09 15.
Article in English | MEDLINE | ID: covidwho-661768

ABSTRACT

Obesity patients are more susceptible to develop COVID-19 severe outcome due to the role of angiotensin-converting enzyme 2 (ACE2) in the viral infection. ACE2 is regulated in the human cells by different genes associated with increased (TLR3, HAT1, HDAC2, KDM5B, SIRT1, RAB1A, FURIN and ADAM10) or decreased (TRIB3) virus replication. RNA-seq data revealed 14857 genes expressed in human subcutaneous adipocytes, including genes mentioned above. Irisin treatment increased by 3-fold the levels of TRIB3 transcript and decreased the levels of other genes. The decrease in FURIN and ADAM10 expression enriched diverse biological processes, including extracellular structure organization. Our results, in human subcutaneous adipocytes cell culture, indicate a positive effect of irisin on the expression of multiple genes related to viral infection by SARS-CoV-2; furthermore, translatable for other tissues and organs targeted by the novel coronavirus and present, thus, promising approaches for the treatment of COVID-19 infection as therapeutic strategy to decrease ACE2 regulatory genes.


Subject(s)
Adipocytes/drug effects , Fibronectins/pharmacology , Gene Expression Regulation/drug effects , ADAM10 Protein/genetics , ADAM10 Protein/metabolism , Adipocytes/cytology , Adipocytes/metabolism , Amyloid Precursor Protein Secretases/genetics , Amyloid Precursor Protein Secretases/metabolism , Angiotensin-Converting Enzyme 2 , Betacoronavirus/genetics , Betacoronavirus/metabolism , COVID-19 , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cells, Cultured , Coronavirus Infections/virology , Fibronectins/genetics , Fibronectins/metabolism , Furin/genetics , Furin/metabolism , Gene Ontology , Histone Acetyltransferases/genetics , Histone Acetyltransferases/metabolism , Histone Deacetylase 2/genetics , Histone Deacetylase 2/metabolism , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Models, Biological , Molecular Sequence Annotation , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Obesity/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/virology , /genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism , SARS-CoV-2 , Signal Transduction , Sirtuin 1/genetics , Sirtuin 1/metabolism , Toll-Like Receptor 3/genetics , Toll-Like Receptor 3/metabolism , rab1 GTP-Binding Proteins/genetics , rab1 GTP-Binding Proteins/metabolism
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