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1.
PLoS Pathog ; 17(3): e1009392, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33760889

RESUMO

Coronavirus interaction with its viral receptor is a primary genetic determinant of host range and tissue tropism. SARS-CoV-2 utilizes ACE2 as the receptor to enter host cell in a species-specific manner. We and others have previously shown that ACE2 orthologs from New World monkey, koala and mouse cannot interact with SARS-CoV-2 to mediate viral entry, and this defect can be restored by humanization of the restrictive residues in New World monkey ACE2. To better understand the genetic determinants behind the ability of ACE2 orthologs to support viral entry, we compared koala and mouse ACE2 sequences with that of human and identified the key residues in koala and mouse ACE2 that restrict viral receptor activity. Humanization of these critical residues rendered both koala and mouse ACE2 capable of binding the spike protein and facilitating viral entry. Our study shed more lights into the genetic determinants of ACE2 as the functional receptor of SARS-CoV-2, which facilitates our understanding of viral entry.


Assuntos
/enzimologia , Peptidil Dipeptidase A/genética , Receptores Virais/genética , /fisiologia , Animais , Sequência de Bases , Especificidade de Hospedeiro , Humanos , Camundongos/genética , Camundongos/virologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Phascolarctidae/genética , Phascolarctidae/virologia , Receptores Virais/metabolismo , Alinhamento de Sequência , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus
2.
Adv Exp Med Biol ; 1321: 53-68, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33656713

RESUMO

Following the outbreaks of SARS-CoV in 2002 and MERS-CoV in 2012, the COVID-19 pandemic caused by the SARS-CoV-2 virus has become an increasing threat to human health around the world. Numerous studies have shown that SARS-CoV-2 appears similar to the SARS-CoV as it uses angiotensin converting enzyme 2 (ACE2) as a receptor to gain entry into cells. The main aims of this scoping review were to identify the primary hosts of coronaviruses, the relationship between the receptor binding domain of coronaviruses and ACE2, the organ specificity of ACE2 expression compared with clinical manifestations of the disease, and to determine if this information can be used in the development of novel treatment approaches for the COVID-19 pandemic.


Assuntos
Pandemias , Humanos , Peptidil Dipeptidase A/genética , Glicoproteína da Espícula de Coronavírus
3.
Adv Exp Med Biol ; 1321: 139-146, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33656720

RESUMO

In the continuing COVID-19 pandemic, one of the most important concerns in reproductive health is the issue of male fertility of recovered patients. In this study, we discuss the potential mechanisms that justify the possible impact of COVID-19 on male fertility. The main point of entry of SARS-CoV-2 into the host cells appears to be through the viral spike protein which permits entry into cells via the angiotensin-converting enzyme 2 (ACE2 receptor). In human testes, ACE2 is enriched in Sertoli and Leydig cells and spermatogonia. Also, it seems that there is a mild or severe cytokine storm in patients with severe COVID-19, and such changes may affect fertility. It should also be mentioned that the orchitis caused by the SARS-CoV-2 virus may have an important impact on fertility. Prolonged and high fever may lead to changes in testicular temperature and destroy germ cells. In general, there is little evidence for a definite conclusion, but there are facts that suggest that COVID-19 may affect male fertility. It is prudent for men of reproductive age who have recovered from COVID-19 to be evaluated for the presence of the virus in semen and fertility-related items. There is an urgent need to conduct quality studies on, in particular, the long-term effects of COVID-19 on the fertility of recovered males.


Assuntos
Pandemias , Fertilidade , Humanos , Masculino , Peptidil Dipeptidase A , Testículo
4.
Adv Exp Med Biol ; 1321: 335-342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33656738

RESUMO

Theoretically, human testes are highly expressive organs for angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. This study aimed to investigate whether the causative agent of COVID-19 is found in semen. The databases of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar were searched using a combination of related keywords. All studies with original data, involving detection of SARS-CoV-2 in semen of male patients with COVID-19 or in those who have recovered from it, were included in the study. Six articles, including 136 samples, entered the systematic review. Most of the studies were performed in the recovery phase of COVID-19. In four articles, SARS-CoV-2 was not detected in semen, while in the other two articles semen testing showed the presence of the virus in some samples. Testicular discomfort, testicular cell damage, and spermogram disruption were also reported in some studies. We conclude that the study question cannot be answered with this number of studies. Since most of the samples were mild to moderate forms of COVID-19, it is not yet clear what the presence of the virus in semen will be in severe cases. The long-term effects are also vague. More original articles with better design and in different phases of the disease are needed to draw robust conclusions.


Assuntos
Líquidos Corporais , Humanos , Masculino , Peptidil Dipeptidase A , Sêmen , Testículo
5.
Curr Hypertens Rep ; 23(4): 17, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33768439

RESUMO

PURPOSE OF REVIEW: This review focuses on the associations between the renin-angiotensin system, hypertension, and severe acute respiratory syndrome (SARS-COV-2) infection. A brief prelude on the current state of affairs with COVID-19 is given. In addition to an overview of ACE2, Ang II, and Ang (1-7), this review presents a brief statement on hypertension, including the function of enzymes involved in the control of hypertension, cardiovascular disease, diabetes mellitus, and other malignancies. RECENT FINDINGS: There is currently no data in support of the concerns raised with the use of ACEIs/ARBs. Many researchers have voiced concerns that the use of ACEIs and ARBs may increase tissue ACE2 levels. These researchers therefore recommend that individuals on ACEIs/ARB's medications withhold such antihypertensive drugs, unless advised by their physicians to do so. SARS-CoV-2 uses ACE2 receptors as the port of entry to human hosts. ACE2 and ACE are different enzymes and ACE inhibitors do not inhibit ACE2. Therefore, the use of ARB's or ACEIs should not be discontinued if an individual is infected by SARS-CoV-2. Further studies are required to investigate the effect of ACEIs and ARBs on ACE2 expression and COVID-19.


Assuntos
Hipertensão , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina
6.
Proc Natl Acad Sci U S A ; 118(12)2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33658332

RESUMO

The pandemic of COVID-19, caused by SARS-CoV-2, is a major global health threat. Epidemiological studies suggest that bats (Rhinolophus affinis) are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of host range and cross-species transmission. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor to enter host cells in a species-dependent manner. In this study, we characterized the ability of ACE2 from diverse species to support viral entry. By analyzing the conservation of five residues in two virus-binding hotspots of ACE2 (hotspot 31Lys and hotspot 353Lys), we predicted 80 ACE2 proteins from mammals that could potentially mediate SARS-CoV-2 entry. We chose 48 ACE2 orthologs among them for functional analysis, and showed that 44 of these orthologs-including domestic animals, pets, livestock, and animals commonly found in zoos and aquaria-could bind the SARS-CoV-2 spike protein and support viral entry. In contrast, New World monkey ACE2 orthologs could not bind the SARS-CoV-2 spike protein and support viral entry. We further identified the genetic determinant of New World monkey ACE2 that restricts viral entry using genetic and functional analyses. These findings highlight a potentially broad host tropism of SARS-CoV-2 and suggest that SARS-CoV-2 might be distributed much more widely than previously recognized, underscoring the necessity to monitor susceptible hosts to prevent future outbreaks.


Assuntos
/genética , Receptores Virais/genética , /genética , /metabolismo , Animais , /metabolismo , Especificidade de Hospedeiro , Humanos , Pandemias/prevenção & controle , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Filogenia , Ligação Proteica , Receptores Virais/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Tropismo Viral , /prevenção & controle , Ligação Viral , Internalização do Vírus
8.
Clin Sci (Lond) ; 135(3): 535-554, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33533405

RESUMO

The renin-angiotensin system (RAS) has currently attracted increasing attention due to its potential function in regulating energy homeostasis, other than the actions on cellular growth, blood pressure, fluid, and electrolyte balance. The existence of RAS is well established in metabolic organs, including pancreas, liver, skeletal muscle, and adipose tissue, where activation of angiotensin-converting enzyme (ACE) - angiotensin II pathway contributes to the impairment of insulin secretion, glucose transport, fat distribution, and adipokines production. However, the activation of angiotensin-converting enzyme 2 (ACE2) - angiotensin (1-7) pathway, a novel branch of the RAS, plays an opposite role in the ACE pathway, which could reverse these consequences by improving local microcirculation, inflammation, stress state, structure remolding, and insulin signaling pathway. In addition, new studies indicate the protective RAS arm possesses extraordinary ability to enhance brown adipose tissue (BAT) activity and induces browning of white adipose tissue, and consequently, it leads to increased energy expenditure in the form of heat instead of ATP synthesis. Interestingly, ACE2 is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is threating public health worldwide. The main complications of SARS-CoV-2 infected death patients include many energy metabolism-related chronic diseases, such as diabetes. The specific mechanism leading to this phenomenon is largely unknown. Here, we summarize the latest pharmacological and genetic tools on regulating ACE/ACE2 balance and highlight the beneficial effects of the ACE2 pathway axis hyperactivity on glycolipid metabolism, as well as the thermogenic modulation.


Assuntos
/metabolismo , Doenças Metabólicas/enzimologia , /genética , Animais , /metabolismo , Metabolismo Energético , Humanos , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Doenças Metabólicas/virologia , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina , /fisiologia
10.
Iran J Allergy Asthma Immunol ; 20(1): 11-23, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33639626

RESUMO

The Coronavirus disease 2019 (COVID-19) virus spread from Wuhan, China, in 2019 and is spreading rapidly around the world. COVID-19 victims are almost associated with cardiovascular disease, high blood pressure, diabetes, and other underlying diseases. Concerning the high prevalence of these disorders, widespread mortality threatens global society, and its fatality rate may increase with increasing COVID-19 prevalence in countries with older populations. Therefore, evaluating patients' clinical status with severe COVID-19 infection and their medical history can help manage treatment. Currently, one of the considered treatments is angiotensin-converting enzyme 2 (ACE2) inhibition. This study investigated virus entry mechanisms through membrane receptors, their role in the pathogenesis of COVID-19 and underlying diseases, and treatment methods based on the viral entrance inhibition. According to existing studies, inhibition of ACE2 can increase oxidative stress, inflammation, fibrosis and ultimately exacerbate underlying diseases such as cardiovascular disease, kidney disease, diabetes, and hypertension in individuals with COVID-19. The ACE2 inhibition is not suitable for patients with COVID-19 with underlying diseases, but it seems that the recombinant ACE2 solution is more appropriate for inhibiting the virus in these patients if hypotension would be monitored.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antivirais/uso terapêutico , /virologia , Internalização do Vírus/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Hipotensão/etiologia , Hipotensão/prevenção & controle , Monitorização Fisiológica , Peptidil Dipeptidase A/metabolismo
11.
Eur J Endocrinol ; 184(4): 543-552, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33539316

RESUMO

Objective: While evidence on the interface between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing. Design and methods: In this exploratory study, we prospectively included adult patients (aged ≥ 18 years) admitted between February 26 and April 30, 2020 to a tertiary care hospital in Switzerland. We assessed the association of an underlying SARS-CoV-2 infection and equilibrium serum levels of RAAS peptides in hospitalized COVID-19 patients 1:1 propensity-score matched with patients suffering from SARS-CoV-2-negative respiratory infections. Subgroup analyses involved stratification for taking RAAS inhibitors. Results: COVID-19 patients had about 50% lower equilibrium serum RAAS peptide levels as compared with matched controls (angiotensin I: 31.6 vs 66.8 pmol/L, -52.7% (95%CI: -68.5% to -36.9%); angiotensin II: 37.7 vs 92.5 pmol/L, -59.2% (95%CI: -72.1% to -46.3%); angiotensin (1-5): 3.3 vs 6.6 pmol/L, -49.7% (95%CI: -59.2% to -40.2%); angiotensin (1-7): 4.8 vs 7.6 pmol/L, -64.9% (95%CI: -84.5% to -45.3%)). While the plasma renin activity was lower in COVID-19 patients (88.6 vs 207.9 pmol/L, -58.5% (95%CI: -71.4% to -45.6%)), there was no difference of angiotensin-converting enzyme (ACE) and ACE2 plasma activity between the groups. Subgroup analyses revealed a pronounced RAAS peptide profile depression in COVID-19 patients among those not on RAAS inhibitors. Conclusions: As compared with SARS-CoV-2-negative patients, we found a downregulated RAAS in presence of a SARS-CoV-2 infection. Whether the lower levels of the protective angiotensin (1-5) and (1-7) are linked to adverse outcomes in COVID-19 warrants further investigation.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , /sangue , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Renina/sangue , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema Renina-Angiotensina
12.
Bratisl Lek Listy ; 122(3): 206-211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33618530

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has become a serious public health problem for    183 out of 197 countries in the world. Understanding the routes and pathogenesis of the coronavirus is important and it is considered that the studies on host cell receptor Angiotensin Converting Enzyme 2 (ACE2) may be valuable for the treatment and prevention of the disease. AIM: To evaluate the possibility of inhibition of SARS-CoV-2 at throat. METHODS: A comprehensive literature search was conducted. CONCLUSION: In view of the fact that the mouth and nose have higher number of ACE2 expressed cells, they serve as a gateway for the virus to enter. Thus, blocking the gate could be a good choice to reduce or even prevent the transmission. Small interfering RNAs (siRNAs) are double-stranded RNA molecules and could be designed easily and directed against many strains of a virus. Due to their features, siRNAs can provide a potential strategy to interfere with the replication of viral diseases. We think that since oral and nasal epithelial cells are relatively easily accessible it may allow to develop siRNA molecules to inhibit SARS-CoV-2 already at the entry where it continues to replicate for a period (Fig. 1, Ref. 50).


Assuntos
Infecções por Coronavirus , Humanos , Peptidil Dipeptidase A/genética , Faringe
13.
Food Chem ; 351: 129290, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33631613

RESUMO

The effect of different types of sugar (sucrose, demerara, brown, fructose, coconut sugar, and honey) on sheep milk kefir was evaluated. Microbial counts (Lactobacillus, Lactococcus, Leuconostoc, yeast), antagonistic activity against foodborne pathogens, microstructure (scanning electron microscopy), and antiproliferative activity of cancer cells were evaluated. Furthermore, the antioxidant activity (DPPH), inhibitory activity of angiotensin-converting enzyme (ACE), α-amylase, and α-glucosidase, lactose content, lactic and acetic acids and ethanol, fatty acid profile and volatile organic compounds were determined. The addition of sugars increased the Lactobacillus population (up to 2.24 log CFU/mL), metabolites concentration, antagonistic activity against pathogens, antioxidant activity (11.1 to 24.1%), ACE inhibitory activity (27.5 to 37.6%), α-amylase inhibition (18 to 37.4%), and anti-proliferative activity. Furthermore, it improved the fatty acid profile and volatile compounds. The results suggest that the replacement of sucrose with different types of sugar constitute an interesting option to be used in sheep milk kefir formulations.


Assuntos
Kefir/análise , Sacarose/química , Animais , Antioxidantes/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Kefir/microbiologia , Kefir/toxicidade , Lactobacillus/isolamento & purificação , Lactobacillus/metabolismo , Lactococcus/isolamento & purificação , Lactococcus/metabolismo , Leite/química , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Análise de Componente Principal , Ovinos , Compostos Orgânicos Voláteis/análise , Leveduras/isolamento & purificação , Leveduras/metabolismo , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo
14.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431535

RESUMO

A 27-year-old woman presented to the dermatology department with a 1-year history of multiple asymptomatic violaceous lesions on her upper and lower extremities, trunk and abdomen. The lesions were firm on palpation. She had no other associated symptoms and the rest of the examination was unremarkable. An incisional biopsy showed multiple confluent granulomas composed of histiocytes devoid of necrosis surrounded by a rim of lymphocytes extending to the subcutaneous fat consistent with the diagnosis of subcutaneous sarcoidosis. The serum ACE assay was elevated at 134 IU/L. Other blood tests including complete blood count, renal and liver function tests, serum calcium and phosphate were within normal ranges and chest X-ray was unremarkable. Complete remission was achieved with an intralesional triamcinolone injection (10 mg/mL) for a few sessions. Subcutaneous sarcoidosis is a rare variation and its diagnosis requires a high index of suspicion.


Assuntos
Sarcoidose/diagnóstico , Dermatopatias/diagnóstico , Triancinolona/administração & dosagem , Adulto , Doenças Assintomáticas/terapia , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Injeções Intralesionais , Peptidil Dipeptidase A/análise , Sarcoidose/sangue , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Pele/patologia , Dermatopatias/sangue , Dermatopatias/tratamento farmacológico , Dermatopatias/patologia , Resultado do Tratamento
15.
Herz ; 46(2): 107-114, 2021 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-33394058

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic is a challenge for our healthcare system but at the same time is one of the excellent catalyzers and promoters of successful translational research. The COVID-19 is not only a simple viral infection of the bronchial system but is also a pandemic hyperinflammatory multiorgan disease. The cardiovascular system plays a causal role in this context, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades host cells via the angiotensin-converting enzyme 2 (ACE-2), an enzyme in the renin-angiotensin system. Furthermore, cardiovascular comorbidities and risk factors, such as hypertension, diabetes and obesity play an important role in the severity of the course of the disease. Additional risk factors, such as gender, age, genetics and air pollution modulate both the severity of the SARS-CoV­2 infection as well as cardiovascular diseases. As sequelae of COVID-19, increased thrombosis, myocardial infarction, myocardial inflammation and vasculitis occur, which directly damage the cardiovascular system and substantially contribute to the high morbidity and mortality. Knowledge gained from many studies on the course of the disease in patients infected with SARS-CoV­2 has led to improved treatment possibilities, which now in the second wave are partly standardized and were, and are, in particular adapted to complications of the cardiovascular system. In this review we provide a short overview on the pathophysiology of the SARS-CoV­2 in general and also specifically on the cardiovascular system. Furthermore, we summarize the current treatment approaches and their pathophysiological principles (status November 2020).


Assuntos
Doenças Cardiovasculares , Doenças Cardiovasculares/terapia , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina
17.
Environ Res ; 195: 110722, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33422505

RESUMO

Coronavirus disease (COVID-19) is currently a serious global issue. Epidemiological studies have identified air pollutants, including particulate matter (PM), as a risk factor for COVID-19 infection and severity of illness, in addition to numerous factors such as pre-existing conditions, aging and smoking. However, the mechanisms by which air pollution is involved in the manifestation and/or progression of COVID-19 is still unknown. In this study, we used a mouse model exposed to crude PM, collected by the cyclone method, to evaluate the pulmonary expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2), the two molecules required for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. Multiplex immunohistochemical analysis revealed that exposure to PM increased the expression of these two molecules at the same site. Furthermore, image cytometry analysis revealed increased expression of these proteins, particularly, in the alveolar type 2 cells and macrophages, which are potential targets for SARS-CoV-2. Our findings provide an experimental evidence that exposure to PM may adversely affect the manifestation and progression of COVID-19, mediated by the impact of SARS-CoV-2 on the site of entry. The study results suggest that examining these effects might help to advance our understanding of COVID-19 and aid the development of appropriate social interventions.


Assuntos
Peptidil Dipeptidase A , Animais , Humanos , Pulmão , Camundongos , Material Particulado/toxicidade , Peptidil Dipeptidase A/genética , Serina Endopeptidases/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-33503828

RESUMO

While COVID-19 infection and mortality rates are soaring in Western countries, Southeast Asian countries have successfully avoided the second wave of the SARS-CoV-2 pandemic despite high population density. We provide a biochemical hypothesis for the connection between low COVID-19 incidence, mortality rates, and high visceral adiposity in Southeast Asian populations. The SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a gateway into the human body. Although the highest expression levels of ACE2 are found in people's visceral adipose tissue in Southeast Asia, this does not necessarily make them vulnerable to COVID-19. Hypothetically, high levels of visceral adiposity cause systemic inflammation, thus decreasing the ACE2 amount on the surface of both visceral adipocytes and alveolar epithelial type 2 cells in the lungs. Extra weight gained during the pandemic is expected to increase visceral adipose tissue in Southeast Asians, further decreasing the ACE2 pool. In contrast, weight gain can increase local inflammation in fat depots in Western people, leading to worse COVID-related outcomes. Because of the biological mechanisms associated with fat accumulation, inflammation, and their differential expression in Southeast Asian and Western populations, the second wave of the pandemic may be more severe in Western countries, while Southeast Asians may benefit from their higher visceral fat depots.


Assuntos
/epidemiologia , Gordura Intra-Abdominal/fisiologia , Obesidade/complicações , Pandemias , Adiposidade , Ásia Sudeste , Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Humanos , Incidência , Inflamação , Obesidade/epidemiologia , Peptidil Dipeptidase A
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