Epicardial and pericoronary adipose tissue in severe COVID-19 infection.

OBJECTIVE: To investigate the association between epicardial and pericoronary adipose tissue thicknesses measured with computed tomography (CT) and severity of COVID-19 infection. METHODS: We recruited 504 patients admitted with RT-PCR-proven diagnosis of COVID-19 infection and underwent simultaneous Chest CT scanning. Epicardial adipose tissue thickness (EAT) and pericardial adipose tissue thickness (PCAT) were measured by CT. Comparisons were performed between ICU admitting and non-ICU admitting patients were performed. RESULTS: Of 504 patients, 423 patients were hospitalised in normal wards or followed as outpatient, and 81 patients were admitted to ICU. EAT and PCAT were significantly increased in ICU patients (5.98[5.06-7.13] mm vs. 8.05[6.90-9.89] mm, p < 0.001 and 9.3[7.4-11.5] mm vs. 11.2[10.3-13.2] mm, p < 0.001, respectively). In multiple logistic regression analyses, EAT and PCAT were independent predictors of ICU admission. A cut-off point of 6.64 mm EAT has a sensitivity of 82.7% and a specificity of 66.7% (AUC = 0.789, 95% CI: 0.744-0.833, p < 0.001) and a cut-off point of 9.85 mm PCAT has a sensitivity of 91.4% and a specificity of 61.2% (AUC = 0.744, 95% CI: 0.700-0.788, p < 0.001). CONCLUSION: We found that both increased EAT and PCAT were associated with the severity of COVID-19 infection defined as the need for ICU admission.

Editorial Special Issue: 2021 consortium for trans-pyrenean investigations on obesity and diabetes.

This Special Issue of the Journal of Physiology and Biochemistry contains 7 contributions that have been elaborated in the context of the mini-network "Consortium of Trans-Pyrenean Investigations on Obesity and Diabetes" (CTPIOD), which is on its 18th year of existence. This scientific community, mostly involving research groups from France and Spain, but also open to participants coming from all over the world, is focusing its attention on the prevention and the novel treatments of obesity, diabetes, non-alcoholic fatty liver disease, and other noncommunicable diseases. Accordingly, this special issue covers some nutritional, pharmacologic, and genetic aspects of the current knowledge of metabolic diseases. Some of these papers emerge from the lectures of the 18th Conference on Trans-Pyrenean Investigations in Obesity and Diabetes, organized by the University of Clermont-Ferrand and celebrated online in November 30, 2021.

Adipose tissue, systematic inflammation, and neurodegenerative diseases

Obesity is associated with several diseases, including mental health. Adipose tissue is distributed around the internal organs, acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues. Excessive nutritional intake results in hypertrophy and proliferation of adipocytes, leading to local hypoxia in adipose tissue and changes in these adipokine releases. This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines. The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling, which can generate a neuroinflammatory process. In this review, we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction. We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain, particularly the hypothalamus and hippocampus, and that this is partially responsible for these negative cognitive outcomes. In addition, we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Multivessel Epicardial Coronary Artery Thrombosis after Heart Transplantation

Introduction: Although cardiac allograft vasculopathy (CAV) remains one of the leading causes of graft failure after heart transplantation (HTx), simultaneous thrombosis of multiple epicardial coronary arteries (CA) is an uncommon finding. Case Report: A 43-year-old male patient with non-ischemic dilated cardiomyopathy underwent successful HTx in 2019. The first two years after HTx were uneventful, surveillance endomyocardial biopsies (EMB) did not reveal any rejection episodes, coronary CTA revealed only minimal non-calcified CA plaques. The patient was admitted to hospital due to fever and chest pain in 2021. Immunosuppressive therapy consisted of tacrolimus, mycophenolate-mofetil and methylprednisolone. ECG verified sinus rhythm. Laboratory test revealed elevated hsTroponin T, NT-proBNP and CRP levels. Cytomegalovirus, SARS-CoV-2-virus and hemoculture testing was negative. Several high-titre donor-specific HLA class I and II antibodies (DSAs;including complement-binding DQ7) could have been detected since 2020. Echocardiography confirmed mildly decreased left ventricular systolic function and apical hypokinesis. EMB verified mild cellular and antibody-mediated rejection (ABMR) according to ISHLT grading criteria. Cardiac MRI revealed inferobasal and apical myocardial infarction (MI);thus, an urgent coronary angiography was performed. This confirmed thrombotic occlusions in all three main epicardial CAs and in first diagonal CA. As revascularization was not feasible, antithrombotic therapy with acetylsalicylic acid, clopidogrel and enoxaparin was started for secondary prevention. Tests for immune system disorders, thrombophilia and cancer were negative. Patient suddenly died ten days after admission. Necropsy revealed intimal proliferation in all three main epicardial CAs, endothelitis, thrombosis, chronic pericoronary fat inflammation, fat necrosis, and subacute MI. CA vasculitis owing to persistent high-titre DSAs, chronic ABMR and acute cellular and antibody-mediated rejection led to multivessel CA thrombosis and acute multiple MI. ABMR after HTx may be underdiagnosed with traditional pathological methods. Pathologies affecting coronary vasculature of HTx patients with DSAs, unique manifestations of CAV lesions and occlusive thrombosis of non-stenotic, non-atherosclerotic lesions should be emphasized.Copyright © 2023

Comparison of Perindopril vs. Losartan With Regard to Pro-Coagulation Factors in Adipocytes Exposed to Sars-Cov-2 Spike Protein

Background: Obesity is a strong risk factor for more severe Covid-19 infection as adipocytes play an important role in intermediating the spreading, replication, and release of SARS-COV-2. An increase in pro-coagulation factors (tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1)) was observed in Covid-19 patients with moderate to severe symptoms and is reported to be associated with Angiotensin-converting enzyme 2 (ACE2) overexpression. Cardiovascular medications affecting ACE2, such as Perindopril and Losartan, are hypothesized to have an effect on Covid-19 infection-related coagulopathy. This study aims to identify and compare the effect of perindopril and losartan on TF and PAI-1 levels in adipocytes exposed to SARS-COV-2 spike protein. Method(s): Adipocytes were isolated enzymatically from adipose tissue obtained from an obese male donor. Adipocytes were then exposed to SARS-COV-2 S1 spike protein for 24 hours. After exposure, perindopril and losartan were added to the culture medium. ACE2, TF, and PAI-1expression were measured 2 hours later using ELISA. Result(s): SARS-CoV-2 spike protein exposure increased ACE2, TF, and PAI-1 expression. Perindopril addition discernible reduced the tissue factor (TF) expression (4.843 +/- 0.396) compared to a positive control (6.857 +/- 0.228) (p=0.005) but not losartan (5.624 +/- 0.606) (p=0.111). Perindopril was also able to lower PAI-1 expressions (3.484 +/- 0.252) compared to a positive control (4.865 +/- 0.115) (p=0.001), but the losartan did so more effectively (2.633 +/- 0.269) (p=0.000). Conclusion(s): Losartan and perindopril both have the ability to lower pro-coagulation factors, proving the value of ACEIs/ARBs in preventing thrombotic complications in Covid-19 patients.Copyright © 2023

Prevalence and clinical implications of abnormal body composition phenotypes in patients with COVID-19: a systematic review.

BACKGROUND: The impact of body composition (BC) abnormalities on COVID-19 outcomes remains to be determined. OBJECTIVES: We summarized the evidence on BC abnormalities and their relationship with adverse clinical outcomes in patients with COVID-19. METHODS: A systematic search was conducted up until 26 September, 2022 for observational studies using BC techniques to quantify skeletal muscle mass (or related compartments), muscle radiodensity or echo intensity, adipose tissue (AT; or related compartments), and phase angle (PhA) in adults with COVID-19. Methodological quality of studies was assessed using the Newcastle-Ottawa Scale. A synthesis without meta-analysis was conducted to summarize the prevalence of BC abnormalities and their significant associations with clinical outcomes. RESULTS: We included 62 studies (69.4% low risk of bias) with 12-1138 participants, except 3 studies with ≤490,301 participants. Using CT and different cutoff values, prevalence ranged approximately from 22% to 90% for low muscle mass, 12% to 85% for low muscle radiodensity, and 16% to 70% for high visceral AT. Using BIA, prevalence of high FM was 51%, and low PhA was 22% to 88%. Mortality was inversely related to PhA (3/4 studies) and positively related to intra- and intermuscular AT (4/5 studies), muscle echo intensity (2/2 studies), and BIA-estimated FM (2/2 studies). Intensive care unit (ICU) admission was positively related to visceral AT (6/7 studies) and total AT (2/3 studies). Disease severity and hospitalization outcomes were positively related to intra- and intermuscular AT (2/2 studies). Inconsistent associations were found for the rest of the BC measures and hospitalization outcomes. CONCLUSIONS: Abnormalities in BC were prevalent in patients with COVID-19. Although conflicting associations were observed among certain BC abnormalities and clinical outcomes, higher muscle echo intensity (reflective of myosteatosis) and lower PhA were more consistently associated with greater mortality risk. Likewise, high intra- and intermuscular AT and visceral AT were associated with mortality and ICU admission, respectively. This trial was registered at PROSPERO as CRD42021283031.

Elevated FAI Index of Pericoronary Inflammation on Coronary CT Identifies Increased Risk of Coronary Plaque Vulnerability after COVID-19 Infection.

Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.

Mesenchymal Stem Cells: A Potent Cell Source for COVID-19

Coronaviruses are enveloped positive-stranded RNA viruses that cause mild to acute respiratory illness. Coronaviruses can merge envelope proteins with the host cell membranes and de-liver their genetic material. Coronavirus disease 2019 (COVID-19) is the seventh coronavirus clos-est to the severe acute respiratory syndrome (SARS) in bats that infects humans. COVID-19 at-tacks the respiratory system and stimulates the host inflammatory responses, promotes the recruit-ment of immune cells, and enhances angiotensin-converting enzyme 2 (ACE2) activities. Patients with confirmed COVID-19 have experienced fever, dry cough, headache, dyspnea, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral therapy, and renal replacement therapy are commonly used to decrease COVID-19-associated mortality. Inflammation is a common and important factor in the pathogenesis of COVID-19. In recent years, stem cell-based therapies represent a promising therapeutic option against various diseases. Mesenchymal stem cells (MSCs) are multipotent stem cells that can self-renew and differentiate into various tissues of mesodermal ori-gin. MSCs can be derived from bone marrow, adipose tissue, and umbilical cord blood. MSCs, with their unique immunomodulatory properties, represent a promising therapeutic alternative against diseases associated with inflammation. Several previous studies have shown that MSCs with a strong safety profile can improve the treatment of patients with COVID-19. The information in this review provides a summary of the prevention and diagnosis of COVID-19. Also, we focus on the current clinical application of MSCs for treatments of patients with COVID-19.Copyright © 2021 Bentham Science Publishers.

COVID 19 Induced Hyperglycaemic Complications

Background: COVID 19 has two-way interaction with Type II Diabetes Mellitus. First, patient with DM are more prone for developing severe COVID 19. Second, moderate to severe COVID 19 can present with new onset DM or may lead to hyperglycaemia and hyperglycaemic complications in Type II DM patients. In this report we present 4 cases of COVID 19 associated Hyperglycaemic Complication (3 with Diabetic Ketoacidosis and 1 with Hyperglycaemic hyperosmolar state). Method(s): Case Series of patients admitted to Thumbay Hospital, Ajman. Result(s): We report 4 cases of COVID 19 patients who presented to us with hyperglycaemic complications. There of them had features of Diabetic Ketoacidosis and one had Hyperglycaemic hyperosmolar state. All were treated with IV Insulin infusion and IV Fluids. COVID 19 infection was managed as per MOH protocol. All patients recovered well and were discharged in stable condition. Discussion(s): COVID 19 is associated with new onset DM or may lead to hyperglycaemic complications in patients with Type II DM. There are three pathophysiological processes which may be responsible for this finding. One, SARS-CoV-2 virus is known to enter the body through angiotensin-converting enzyme (ACE) II receptors in the pulmonary pneumocytes leading to infection and inflammation. Similar ACE-II receptors are also expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, the small intestine, and the kidneys. Direct infection of pancreatic beta-cells with SARS-CoV-2 virus with beta-cell cell injury is likely the underlying mechanism for development of new onset diabetes and hyperglycaemia in existing diabetic patients. Such direct beta cell infection can cause hyperglycaemic complications in asymptomatic or mild COVID 19 as well. Two, moderate to severe COVID 19 is associated with hyperinflammatory immune response leading to marked rise in inflammatory mediators such as C-reactive protein and ferritin. Such hyperinflammatory response can also lead to hyperglyacemia in patients with diabetes mellitus. Three, corticosteroids are mainstay treatment of patients with moderate to severe COVID 19 and would definitely contribute to worsening of hyperglycaemia in these patients. Our patients presented to us with hyperglycaemic complications before initiation of any treatment. It is likely that such a situation would be due to direct infection and destruction of beta cells with SARS-CoV-2 virus infection. Conclusion(s): Type II Diabetes Mellitus patients are high risk of developing hyperglycaemic complications due to COVID 19. This can lead to increased morbidity and mortality. Patients with Type II DM should seek medical attention even if they have mild to asymptomatic COVID 19 to monitor for hyperglycaemic complication which can develop irrespective of severity of stage of illness.

COVID-19: Could Irisin Become the Handyman Myokine of the 21st Century?

The ongoing Coronavirus disease 2019 (COVID-19) outbreak in China has become the world's leading health headline and is causing major panic and public concerns. After emerging in the City of Wuhan, China, COVID-19 has spread to several countries becoming a worldwide pandemia. Among the studies on COVID-19, it has been demonstrated that novel coronavirus pneumonia is closely associated with inflammatory storms. Controlling the inflammatory response may be as important as targeting the virus. Irisin is a muscle-contraction-induced immunomodulatory myokine related to physical activity. Irisin drives the "browning" of white adipocytes, so enhancing metabolic uncoupling and hence caloric expenditure. Irisin has been clearly shown to be a handyman molecule by exerting beneficial effects on adipose tissues, pancreas, and bone through "cross-talk" between skeletal muscle-adipocyte, skeletal muscle-pancreas, and skeletal muscle-bone, respectively. Irisin has been proposed as a promising strategy for early diagnosis and treatment of various types of cancers, neurological diseases and inflammatory conditions. Irisin has been demonstrated to suppress the immune response, too. The importance of irisin is demonstrated by the increase in the number of scientific papers and patents in recent years. The identification of irisin receptor should greatly facilitate the understanding of irisin's function in exercise and human health. This review examines the structure and recent advances in activi-ties of irisin, suggesting it for further studies on the prevention and cure of COVID-19. Nowadays, studies on irisin plasma levels and physical activity may be useful tools to further investigate the prevention of COVID-19. Irisin may be suggested as a potential novel intervention for COVID-19 by mitigating inflammatory storms, suppressing the immune response and simultaneously alleviating neurological dis-orders such as depression and anxiety.Copyright © 2020 Bentham Science Publishers.

FINUT 2022 Conference Abstracts

The proceedings contain 343 papers. The topics discussed include: alterations in the gut microbiota associated with obesity and metabolic disease: cause or consequence?;childhood obesity in the community context;big data and machine learning as tools for the biomedical field;thermogenesis and adipose tissue: effect of genistein;pediatric obesity and comorbidities: a question of time and genetics? the Portuguese experience;nutrigenomics of inflammation;environmental factors associated with school children's excess of weight in communities of Costa Rica;dietary consumption: guided by a focus of nutrient adequacy or selection of foodstuffs?;functional foods as key regulators of gut microbiota in the SARS-CoV-2 infection;immunomodulatory properties of human milk;vitamin d in childhood and adolescent obesity;and new sources of vitamin D and E supplementation during pregnancy.

Total Stromal Fraction (TSF)-Fortified Adipose Tissue-Derived Stem Cells Source: An Emerging Regenerative Realm Against COVID-19 In-duced Pulmonary Compromise

The inception of the COVID-19 pandemic has jeopardized humanity with markedly dam-pening of worldwide resources. The viral infection may present with varying signs and symptoms, imitating pneumonia and seasonal flu. With a gradual course, this may progress and result in the deadliest state of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). More-over, following recovery from the severe brunt of COVID-19 infection, interstitial portions of alve-oli have been found to undergo residual scarring and further to have compromised air exchange. Such alterations in the lung microenvironment and associated systemic manifestations have been recognized to occur due to the extensive release of cytokines. The mortality rate increases with advancing age and in individuals with underlying co-morbidity. Presently, there is no availability of specific antiviral therapy or any other definitive modality to counter this progressive worsening. However, we believe principles and advancing cell-based therapy may prove fruitful in subjugating such reported worsening in these patients. This article reviews eminent knowledge and relevant ad-vancements about the amelioration of lung damage due to COVID-19 infection using adipose tis-sue-derived-total stromal fraction (TSF).Copyright © 2022 Bentham Science Publishers.

Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction.

In order to explore the proteomic signatures of epicardial adipose tissue (EAT) related to the mechanism of heart failure with reduced and mildly reduced ejection fraction (HFrEF/HFmrEF) and heart failure (HF) with preserved ejection fraction (HFpEF), a comprehensive proteomic analysis of EAT was made in HFrEF/HFmrEF (n = 5) and HFpEF (n = 5) patients with liquid chromatography-tandem mass spectrometry experiments. The selected differential proteins were verified between HFrEF/HFmrEF (n = 20) and HFpEF (n = 40) by ELISA (enzyme-linked immunosorbent assay). A total of 599 EAT proteins were significantly different in expression between HFrEF/HFmrEF and HFpEF. Among the 599 proteins, 58 proteins increased in HFrEF/HFmrEF compared to HFpEF, whereas 541 proteins decreased in HFrEF/HFmrEF. Of these proteins, TGM2 in EAT was down-regulated in HFrEF/HFmrEF patients and was confirmed to decrease in circulating plasma of the HFrEF/HFmrEF group (p = 0.019). Multivariate logistic regression analysis confirmed plasma TGM2 could be an independent predictor of HFrEF/HFmrEF (p = 0.033). Receiver operating curve analysis indicated that the combination of TGM2 and Gensini score improved the diagnostic value of HFrEF/HFmrEF (p = 0.002). In summary, for the first time, we described the proteome in EAT in both HFpEF and HFrEF/HFmrEF and identified a comprehensive dimension of potential targets for the mechanism behind the EF spectrum. Exploring the role of EAT may offer potential targets for preventive intervention of HF.

COVID-19 and liver injury in individuals with obesity.

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage.

In vitro studies of the renin-angiotensin system in human adipose tissue/adipocytes and possible relationship to SARS-CoV-2: a scoping review.

The renin-angiotensin system (RAS) operates within adipose tissue. Obesity-related changes can affect adipose RAS, predisposing to hypertension, type 2 diabetes, and possibly severe COVID-19. We evaluated the in vitro research on human adipose RAS and identified gaps in the literature. Medline (Ovid), Embase (Ovid), Web of Science, Scopus, and 1findr were searched to identify relevant studies. Fifty primary studies met our inclusion criteria for analysis. Expression of RAS components (n = 14), role in differentiation (n = 14), association with inflammation (n = 15) or blood pressure (n = 7) were investigated. We found (1) obesity-related changes in RAS were frequently studied (30%); (2) an upswing of articles investigating adipose ACE-2 expression since the COVID-19 pandemic; (3) a paucity of papers on AT2R and Ang (1-7)/MasR which counterbalance Ang II/ART1; (4) weight loss lowered adipose ACE-2 mRNA expression; and (5) angiotensin receptor blockers (ARBs) reduced deleterious effects of angiotensin II. Overall, these studies link Ang II/ATR1 signalling to impaired adipogenesis and a pro-inflammatory dysfunctional adipose tissue, with ATR1 blockade limiting these responses. ACE-2 may mitigate Ang II effects by converting it to Ang(1-7) which binds MasR. More work is needed to understand adipose RAS in various pathologic states such as obesity and COVID-19 infection.T.

What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?

Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID. The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID. The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokines, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review. It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomena which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.

What is the role of brown adipose tissue in metabolic health: lessons learned and future perspectives in the long COVID?

Metabolic physiology plays a key role in maintaining our health and resilience. Metabolic disorders can lead to serious illnesses, including obesity. The pathogenesis of the new long COVID syndrome in individuals with long-term recovery after SARS-Co-2 infection is still incomplete. Thus there is growing attention in the study of adipose tissue activities, especially brown adipose tissue (BAT) and associated resilience which plays a crucial role in different types of obesity as potential targets for pharmacologic and nutritional interventions in the context of obesity and long COVID. The number of studies examining mechanisms underlying BAT has grown rapidly in the last 10 years despite of role of BAT in individuals with COVID-19 and long COVID is modest. Therefore, this review aims to sum up data examining BAT activities, its resilience in health, obesity, and the possible link to long COVID. The search was conducted on studies published in English mostly between 2004 and 2022 in adult humans and animal models. Database searches were conducted using PubMed, Scopus, and Google Scholar for key terms including adipose tissue, BAT, adipokinins, obesity, VPF/VEGF, and pathogenesis. From the initial search through the database were identified relevant articles that met inclusion and exclusion criteria and our data regarding adipose tissues were presented in this review. It will discuss adiposity tissue activities. Current literature suggests that there are BAT integral effects to whitening and browning fat phenomenons which reflect the homeostatic metabolic adaptive ability for environmental demand or survival/adaptive mechanisms. We also review neural and vascular impacts in BAT that play a role in resilience and obesity. Finally, we discuss the role of BAT in the context of long COVID in basic research and clinical research.

Extracellular Vesicles as Carriers of Adipokines and Their Role in Obesity.

Extracellular vesicles (EVs) have lately arisen as new metabolic players in energy homeostasis participating in intercellular communication at the local and distant levels. These nanosized lipid bilayer spheres, carrying bioactive molecular cargo, have somehow changed the paradigm of biomedical research not only as a non-classic cell secretion mechanism, but as a rich source of biomarkers and as useful drug-delivery vehicles. Although the research about the role of EVs on metabolism and its deregulation on obesity and associated pathologies lagged slightly behind other diseases, the knowledge about their function under normal and pathological homeostasis is rapidly increasing. In this review, we are focusing on the current research regarding adipose tissue shed extracellular vesicles including their characterization, size profile, and molecular cargo content comprising miRNAs and membrane and intra-vesicular proteins. Finally, we will focus on the functional aspects attributed to vesicles secreted not only by adipocytes, but also by other cells comprising adipose tissue, describing the evidence to date on the deleterious effects of extracellular vesicles released by obese adipose tissue both locally and at the distant level by interacting with other peripheral organs and even at the central level.