Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19.

Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes. KEY MESSAGES: • SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. • Infection of endocrine organs induces interferon response. • Interferon response is observed in adipose tissue independently of virus presence. • Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. • Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.

Ghrelin and Leptin Concentrations in Patients after SARS-CoV2 Infection.

SARS-CoV2 infection can lead to severe cytokine storm especially in obese patients. Ghrelin acts not only as an appetite regulator but can also play a key role in the immune reaction. Leptin, secreted mainly by the white adipose tissue, can act as a pro-inflammatory cytokine. The crucial question is whether or not the cytokine storm in COVID-19 patients with obesity is linked to adipokine dysregulation. The aim of this study was to assess ghrelin and leptin concentrations in patients 6 months after SARS-CoV2 infection in comparison to a control group considering the influence of sex. The study group included 53 patients with a history of COVID-19 and 87 healthy subjects in the control group. Leptin and ghrelin concentrations as well as hormonal and biochemical parameters were measured. A significantly higher ghrelin concentration was observed in the COVID-19 group in comparison to the control group, with a statistically significant impact of sex on the relationship between COVID-19 and ghrelin concentration, which was lower in the males. No statistically significant differences in leptin concentration were observed between the groups. A significant negative correlation was observed between ghrelin and testosterone and morning cortisol levels in the COVID-19 group. The current study showed that ghrelin levels were significantly higher in patients 6 months after a mild course of SARS-CoV2 infection. To confirm the hypothetical protective role of ghrelin in the inflammatory process, it would be necessary to compare serum ghrelin levels between patients after mild and severe courses of COVID-19. Due to the small sample size and the lack of patients with a severe course of COVID-19, these observations need further investigation. There were no differences in leptin concentrations between the COVID-19 patients and the control group.

Adipokines as Diagnostic and Prognostic Markers for the Severity of COVID-19.

Accumulating evidence implicates obesity as a risk factor for increased severity of disease outcomes in patients infected with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Obesity is associated with adipose tissue dysfunction, which not only predisposes individuals to metabolic complications, but also substantially contributes to low-grade systemic inflammation, altered immune cell composition, and compromised immune function. This seems to impact the susceptibility and outcome of diseases caused by viruses, as obese people appear more vulnerable to developing infections and they recover later from infectious diseases than normal-weight individuals. Based on these findings, increased efforts to identify suitable diagnostic and prognostic markers in obese Coronavirus disease 2019 (COVID-19) patients to predict disease outcomes have been made. This includes the analysis of cytokines secreted from adipose tissues (adipokines), which have multiple regulatory functions in the body; for instance, modulating insulin sensitivity, blood pressure, lipid metabolism, appetite, and fertility. Most relevant in the context of viral infections, adipokines also influence the immune cell number, with consequences for overall immune cell activity and function. Hence, the analysis of the circulating levels of diverse adipokines in patients infected with SARS-CoV-2 have been considered to reveal diagnostic and prognostic COVID-19 markers. This review article summarizes the findings aimed to correlate the circulating levels of adipokines with progression and disease outcomes of COVID-19. Several studies provided insights on chemerin, adiponectin, leptin, resistin, and galectin-3 levels in SARS-CoV-2-infected patients, while limited information is yet available on the adipokines apelin and visfatin in COVID-19. Altogether, current evidence points at circulating galectin-3 and resistin levels being of diagnostic and prognostic value in COVID-19 disease.

Inflammatory Pathways Associated with Covid-19 Severity Differ Based on Obesity Status

Background: Severe COVID-19 and obesity are characterized by higher inflammation. We aimed to examine early inflammatory patterns in people with (Ob) and without (NOb) obesity and COVID-19 and how they relate to COVID-19 disease severity Methods: Ob (BMI >30 Kg/m2) and NOb with COVID-19 matched for age, sex and WHO disease severity provided blood early after diagnosis. Immunoassays measured 57 plasma biomarkers reflecting innate immune and endothelial activation, systemic inflammation, coagulation, metabolism and microbial translocation (Fig 1). Between-group differences were assessed by Mann- Whitney. Associations between subsequent maximal COVID-19 severity (mild vs moderate/severe/critical) and biomarkers were explored by logistic regression adjusted for age, sex, hypertension (HTN) and diabetes (DM). Data are median pg/mL [IQR] or n [%] unless stated Results: Of 100 subjects (50 Ob and 50 Nob) presenting between April 2020 and March 2021, characteristics (Ob vs Nob) included: age 65 [23-91] vs 65 [21-95];female sex 27 (48%) vs 28 (56%);BMI 33.7 [30.0-71.8] vs 23.3 [15.3-25.9];disease severity mild 22 [48%] vs 23 [46%], moderate 15 [30%] vs 13 [26%], severe 6 [12%] vs 7 [14%];HTN 30 (60%) vs 17 (34%);DM 19 [38%] vs 6 [12%];days from symptom onset 7 [2-17] vs 8 [1-15];vaccinated 3 (6%) vs 0 (0%). Compared to NOb, Ob had higher IFN-alpha (1.8 [0.6;11] vs 0.9 [0.1;4.7]), CRP (10 mAU/mL [9.6;10.2] vs 9.7 [7.2;10]), IL-1RA (197 [122;399] vs 138 [88;253]), IL-4 (288 AU/mL [161;424] vs 205 [82;333]), vWF (252 [166;383] vs 163 [96;318]), Zonulin (114 ng/mL [77;131] vs 57 [18;106]), Resistin (956 [569;1153] vs 727 [712;1525]), Leptin (3482 [1513;5738] vs 848 [249;2114]), and lower Adiponectin (1.12 mg/L [0.09;1.5] vs 1.5 [1.18;1.93]), all p< 0.05. In both groups higher, proinflammatory IL-18 and lower levels of antiinflammatory CCL22 and IL-5 were associated with higher odds of disease severity, and lower E-selectin with higher disease severity only in Ob. However, in NOb higher type 3 interferons (IL-28A), macrophage activation (sCD163, CCL3) and vascular inflammation markers (ICAM-1, VCAM-1), along with higher S100B, GM-CSF and leptin were also associated with disease severity, a pattern not observed in Ob (Fig 1) Conclusion(s): Although Ob had higher overall levels of inflammation than NOb, few biomarkers predicted subsequent COVID-19 severity in Ob. These differential inflammatory patterns suggest dysregulated immune responses in Ob with COVID-19. (Figure Presented).

Adipokines levels in hospitalized patients for COVID-19 and their role in prognosis

Introduction and Aim: Adipokines, both pro-inflammatory and anti-inflammatory ones, play an important role in regulation of inflammatory responses toward infections including COVID-19. The aim of the study was to investigate the role of chemerin, adiponectin and leptin concentrations in prognosis and clinical features of hospitalized COVID19 patients. Method(s): Serum levels of 3 adipokines were measured upon admission of 77 PCR-confirmed COVID-19 patients who were followed up for 6 months and grouped into 2 according to prognosis. Result(s): A total of 77 patients were included in the study. 58.4% of patients were male and the average age was 63.2+/- 18.3 years (R: 21-96). 51 patients (66.2%) had a good prognosis based on 6-month follow-up. Leucocyte number, neutrophil to lymphocyte ratio, GGT, ALP, D-Dimer, ferritin, CRP, prokalsitonin, CK, troponin, oxygen saturation at admission, presence of comorbidities or another infection were all signifactly related with prognosis of disease (p<0.05). Among adipokines only Chemerin was significantly higher in the bad prognosis group (p=0.044) and the serum levels showed a negative correlation with age (p=0.037). Leptin levels were correlated negatively with GGT levels which were significantly higher in bad prognostic group (p=0.036). The ratio of adipokines had no relation with the prognosis and the other clinical features. Conclusion(s): Higher Chemerin levels, an anti-inflammatory adipokine, were related with a worse prognosis, whereas GGT levels especially higher in bad prognostic group were shown to be inversely correlated with leptin levels (a pro-inflammatory adipokine). Anti-inflammatory response predominance at admission might be a bad prognostic clue.

The Impact of LEP rs7799039 Polymorphism and Obesity on the Severity of Coronavirus Disease-19.

Background and Aims: SARS-CoV-2 infection has been recorded in 230 countries to date. Obesity has a negative impact on one's quality of life and is one of the main causes of mortality globally. Obesity affects the immune system, making the host more susceptible to infectious infections. Also, obesity commonly provokes the severity of respiratory diseases so the correlation of LEP rs7799039 Polymorphism in corpulent patients with COVID-19 infection was clearly investigated in the current study. Methods: A total of 232 patients were recruited, 116 patients were obese with COVID-19 infection, and 116 patients were non obese COVID-19. Fasting blood glucose test (FBG), hemoglobin A1C (HbA1C), complete blood count (CBC), international normalized ratio (INR), urea, alanine transaminase (ALT), aspartate aminotransferase (AST), D dimer and C-reactive protein (CRP) were estimated. C.T. scan was performed for each patient, and C.T. severity score was calculated. Genotyping for the leptin rs7799039 SNPs was performed by TaqMan® (Applied Biosystems Step One TM Real-time PCR). Results: Regarding LEP polymorphism, all individuals of non-obese groups significantly had the homozygous allele GG (100%), whereas only 56% of obese groups had GG alleles (P = 0.001). The severity scores significantly (P = 0.001) varied regarding LEP polymorphism regarding Rs7799039, where the largest proportion of those with Grade IV had the homozygous allele AA (57.1%). Conclusion: There was a correlation between the leptin gene allelic discrimination and COVID-19 CT brutality in obese patients. The A allele was considered a risk factor for severity in COVID-19 patients while the G allele contributes to decreasing that risk.

Exercise modulation in inflammation and metabolic hormonal disorders of COVID-19 to decrease risk factors in coronary heart disease.

OBJECTIVES: Sedentary life style separated during COVID-19 pandemic. Patients with cardiovascular diseases (CVD) are vulnerable with sedentary life style. Therefore, the aim of this study was to investigate the effect of 8 weeks of combined and high intensity interval training (HIIT) on C Reactive protein, galectin-3, leptin, fibrinogen and insulin resistance index in coronary heart disease after COVID-19. METHODS: Thirty-six cardiovascular patients (55.14 ± 1.4 years, 78.6 ± 5.1 kg) were divided into three groups of combined exercise (n=13), HIIT (n=12) and control group (n=11). Combined exercise consisted of aerobic (4 weeks) and aerobic + HIIT exercise (4 weeks), three sessions per weeks. The protocol of the HIIT group included performing high intensity interval training, three sessions per weeks for 8 weeks. Blood samples were taken 24 h before the first training session and 48 h after the last training. C Reactive protein (CRP), galectin-3, leptin, fibrinogen measured with ELISA kit. RESULTS: CRP, galectin-3 and fibrinogen decreased significantly after 8 weeks of combined training and HIIT (compare to pre-test). Also, insulin resistance index after 8 weeks of combined exercise showed a significant decrease compare to pre-test (p<0.05). After 8 weeks, CRP, galectin-3 and insulin resistance significantly decreased compare to control group (p<0.05). CONCLUSIONS: In the patient with CVD, combined exercise training may be more effective than HIIT in reducing metabolic and heart risk factors after an epidemic such as COVID-19. However, change of leptin need to more studies.

Adiponectin, Leptin, and Resistin Are Dysregulated in Patients Infected by SARS-CoV-2.

Obesity, through adipose tissue (AT) inflammation and dysregulation, represents a critical factor for COVID-19; here, we investigated whether serum levels of adiponectin, HMW oligomers, leptin, and resistin are modulated and/or correlated with clinical and biochemical parameters of severe COVID-19 patients. This study included 62 severe COVID-19 patients; 62 age and sex-matched healthy subjects were recruited as a control group. Anthropometric and biochemical parameters were obtained and compared. Adiponectin, HMW oligomers, leptin, and resistin were analyzed by ELISA. The adiponectin oligomerization state was visualized by Western blotting. When compared to healthy subjects, total adiponectin levels were statistically lower in severe COVID-19 while, in contrast, the levels of leptin and resistin were statistically higher. Interestingly, HMW adiponectin oligomers negatively correlated with leptin and were positively associated with LUS scores. Resistin showed a positive association with IL-6, IL-2R, and KL-6. Our data strongly support that adipose tissue might play a functional role in COVID-19. Although it needs to be confirmed in larger cohorts, adiponectin HMW oligomers might represent a laboratory resource to predict patient seriousness. Whether adipokines can be integrated as a potential additional tool in the evolving landscape of biomarkers for the COVID-19 disease is still a matter of debate. Other studies are needed to understand the molecular mechanisms behind adipokine's involvement in COVID-19.

The Use of alpha 1-Adrenergic Receptor Antagonists in the Prevention of Adverse Outcomes of COVID-19 Infection in Obese Patients

Obesity is widely reported to be associated with a higher risk of the severity and worse clinical outcome of COVID-19. With the global prevalence of obesity, exploring the relationship between obesity and the severity of COVID-19 disease is of major clinical importance, thus requiring increased attention to preventive measures in susceptible individuals. Studies have shown that obesity is associated with increased risk of hospitalisation, intensive care unit admission, integrated motivational-volitional requirement and mortality among patients with COVID-19. The pathophysiological mechanisms which cause disease severity and adverse outcomes among obese subjects remain unclear. Recently, it was shown that elevated leptin levels correlate positively with the severity and progression of disease in COVID-19 patients. Leptin modulates both the innate and adaptive immune responses in cells. Elevated leptin levels in obese individuals may contribute to worse symptoms and outcomes in COVID-19 disease. Emerging evidence suggests that alpha-1 (alpha 1)-adrenergic receptor stimulation increases leptin secretion, while the administration of alpha 1-adrenergic receptor antagonists is reported to reduce plasma leptin levels in human subjects. Therefore, alpha 1-adrenergic receptor antagonists may improve clinical outcomes in obesity patients with COVID-19 infection through modulation of hyperinflammation and reduction of plasma leptin levels. The aim of this minireview is to delineate the potential beneficial therapeutic effects of alpha 1-adrenergic receptor antagonists in preventing adverse outcomes of coronavirus infection in obese patients. Large, randomised trials are needed to confirm the beneficial effects and safety profile of the use of alpha 1-adrenergic receptor antagonists in obese patients with COVID-19.

The Potential Effect Of Leptin And Il-6 Levels On Covid-19 Severity In Obese Patients

Background: The obesity is one of the high-risk factors in COVID-19 in severe illness and mortality as the pandemic progresses. The pleotropic Leptin is a polypeptide hormone and secreted by adipose tissues. It acts as a proinflammatory cytokine. Leptin is associated with severe conditions known to cause the risk of COVID-19 severity. Acute changes in calorie intake affect Leptin levels, which in turn are related to the amount of adipose tissue. Interleukin 6 (IL-6) also is a pleiotropic cytokine (184 amino acid) and initiates different inflammatory responses in tissues. The aim of study: The aim of this study is to evaluate the effect of Leptin and IL-6 levels on the COVID-19 severity of an early diagnosis in obese patients infected with COVID-19. Materials and Methods: This case-control study included 60 obese subjects, divided to 30 obese without any chronic disease and not infected with COVID-19, and 30 individuals were infected with COVID-19, with the age ranged between (25-60) years. COVID-19 patients divided into three categories, (13 mild/moderate), (10 severe) and (7 dead). And thirty (20 male and 10 female) apparently healthy subjects as control group. Their age and sex were comparable to the patients. The enzyme-linked immunosorbent assay (ELISA) kits used to measure serum Leptin and IL-6 levels. Results: Leptin concentration and IL-6 concentration were significantly higher in obese COVID-19 patients than the obese without COVID-19 and normal weight control group (11.80 +/- 1.38, 344.23 +/- 70.13 vs 8.64 +/- 1.21, 790.34 +/- 194.29 vs 4.09 +/- 2.15, 138.89 +/- 46.36) respectively. However, especially in dead and severe cases increased levels of IL-6 and Leptin than the mild/moderate cases of obese patients infected with COVID-19. Serum leptin level has a positive significant correlation with levels of IL-6, D-dimer, ferritin and NLR in obese COVID-19 patients group. Conclusions: High circulating IL-6 and Leptin in the obese patients might involve dysregulation of proinflammatory cytokines in obesity and may be used as a useful prognostic tool associated with COVID-19 to predict the SARS-COV-2 severity.

A cross-sectional study on the use of big data for the past H1N1 influenza epidemic in obesity after COVID-19: Focused on the body slimming cream and leptin via DTC gene test.

BACKGROUND: Based on the big data of 2010, 2011, and 2012, when H1N1 influenza was prevalent around the world in the past, this study investigated the obesity rate, weight change, and dietary methods of Korean dieters based on the historical situation of the past H1N1 influenza epidemic in Republic of Korea. This is intended to be the data for utilizing the prognostic evaluation of coronavirus disease-19 (COVID-19). OBJECTIVE: After COVID-19, research on obesity should be conducted systematically, and to prevent obesity, nutrition education, customized inner beauty & cosmetics, and the development of body slimming cream and leptin for proper diet should be done at the national level. This study was conducted to investigate the relationship between methods of weight control, generation, and gender, which have not yet been evaluated in the Korean adult population. METHODS: The cross-sectional study was comprised of 25 534 Korean who participated in the Fifth Korean National Health and Nutrition Examination Survey (KNHNES) conducted in 2010, 2011, and 2012. RESULTS: A 17 876 of the 19 375 respondents 20 years of age or older in the KNHNES answered about diet method. Two thousand and fifty-seven (15.63%) men and 4134 (25.77%) women thought of themselves as fat. However, 11 973 people (66.96%) did not change weight in the past year, 2536 people (14.19%) had increase in weight, and 3.164 (17.70%) reduced weight. A total of 7176 people (48.11%) indicated that they attempted to reduce weight through exercising, while 5553 people (37.23%) did so through reduced food intake. CONCLUSIONS: This study was based on big data at the time of the H1N1 influenza epidemic in Korean population. The results of the present study will be helpful in the development of the body slimming cream and leptin via direct to consumer (DTC) gene test (GT) due to the rapid increase in obesity due to COVID-19 pandemic.

Oleic acid-induced acute lung injury in Ob/Ob mice fed with high-fat-diet exacerbate bile acid uptake and liver injury that was reversed by antagonizing their entry

Background and aims: Acute respiratory distress syndrome (ARDS) is a serious complication of COVID-19 and present in a large percentage of COVID-19 deaths. Many studies suggest that people with obesity are at increased risk of severe COVID-19, however, mechanism on liver-lung axis remains unknown. We aimed to evaluate whether bile acid (BAs) trafficking interfere with acute lung injury (ALI) in animal model with obesity. Method: Leptin deficient (ob/ob) mice fed with high-fat-diet (Ob/Ob HFD) were i.p injected with oleic acid (OA) to induce ALI. To modulate BAs uptake, mice were i.p treated with neutralizing antibody for sodium taurocholate co-transporting polypeptide (NTCP;BAs-transporter). Broncho-alveolar lavage fluid (BALF), lungs, livers and serum were obtained from mice and assessed for inflammatory (HandE staining, ALT and pro-inflammatory panel of cytokines), fibrosis (Sirius red staining, a-smooth muscle actin, collagen and fibronectin) and metabolic (BAs, cholesterol, triglyceride, glucose tolerance test (GTT) and fasting blood sugar (FBS)) profiles. In addition, alveolarcapillary membrane injury of surfactant D (SP-D) and the receptor for advanced glycation end-products (RAGE). BAs trafficking were assessed in primary lung cells and their impact on proliferation and apoptosis were evaluated. Results: Compared to WT-littermates, OA-induced lung injury and was worsened in the in the Ob/Ob HFD in the histopathology outcome. In addition, BALF of the Ob/Ob HFD showed elevated levels of BAs (3- fold;P = 0.002) associated with increased GM-CSF, INF-g, IL-1, IL-6 and IL-8 (p < 0.01). Moreover, Ob/Ob HFD with OA showed elevated serum levels in liver enzymes, lipids, glucose and metabolic markers (p < 0.01). In addition, Ob/Ob HFD livers showed an exacerbated fibrosis profile. NTCP neutralizing antibody in Ob/Ob HFD while inhibited BAs uptake/trafficking in both primary alveolar type II (BALF showed 4-fold increase in BAs) and primary hepatocytes (serum showed 3-fold increase in BAs). SP-D, RAGE and serum metabolic markers were suppressed to normal in line with enhance lung and liver histology and maintaining cell viability. Conclusion: Modulation of BAs trafficking from the liver of obese mice to the lungs could be an important step in the pathogenesis of ALI. Antagonizing BAs uptake may suggest a therapeutic strategy in improving liver-lung axis.

Sleep and alimentation: actions for improving quality of life in times of COVID 19

Introduction: Sleep is characterized as a condition of physical and mental rest, in which the person ignores everything going on around him. There is a scientifically proven association between sleep deprivation and unhealthy eating habits, increasing cases of emotional and uncontrolled eating leading to malnutrition. In addition, a bad night's sleep has been associated with worsening mental health, especially in times of pandemic. Objective: In light of the above, this study aimed to report the experience and stimulate reflection about the results of a poll shared on the social network Instagram with the objective of analyzing the quality of sleep of students at a public higher education institution during the COVID-19 Pandemic. Methods: This is an experience report of the extension group “Sleep and Food in times of Pandemic”, composed of students of nursing, nutrition, medicine and mathematics of a public institution of higher education. The group, through its profile on the social network Instagram, shared a sleep satisfaction scale, where users reported in posts according to the condition of their sleep on a scale between good and bad. The scale was made available publicly and online, so the answers were freely accessible to everyone who followed the group's profile. Results: The project had a large significant reach of participants, since the present was observed through the social media of we can mention Instagram e Facebook, that is, an average of 600 posts observed, of these, 34.5% of students reported having a good night's sleep during the pandemic, while 65.5% responded by pointing out a bad night's sleep. Sleep deprivation is inversely related to the regulation of the circadian cycle, is associated with neuroendocrine and metabolic functions, such as reduced leptin and increased ghrelin, increasing appetite and food intake.In parallel to this, individuals in this stressful situation tend to consume foods that are pleasing to the palate, which usually contain higher amounts of sugar and/or fat, because they serve as comfort for the stress they are going through, but may contribute to the risk of developing obesity, insulin resistance, and cardiovascular disease. Conclusion: Some protective factors can help in this change, such as maintaining a daily routine, practicing physical activity, following a dietary pattern and taking care of sleep hygiene. Finally, we emphasize the need for more studies with a more rigid methodological content.

Mediators of Obesity Do Not Influence SARS-CoV-2 Infection or Activation of Primary Human Lung Microvascular Endothelial Cells In Vitro.

Clinical observations have shown that obesity is associated with the severe outcome of SARS-CoV-2 infection hallmarked by microvascular dysfunction in the lungs and other organs. Excess visceral fat and high systemic levels of adipose tissue (AT) derived mediators such as leptin and other adipokines have also been linked to endothelial dysfunction. Consequently, we hypothesized that AT-derived mediators may exacerbate microvascular dysfunction during of SARS-CoV-2 infection and tested this in a primary human lung microvascular endothelial (HLMVEC) cell model. Our results indicate that HLMVEC are not susceptible to SARS-CoV-2 infection since no expression of viral proteins and no newly produced virus was detected. In addition, exposure to the virus did not induce endothelial activation as evidenced by a lack of adhesion molecule, E-selectin, VCAM-1, ICAM-1, and inflammatory cytokine IL-6 induction. Incubation of endothelial cells with the pro-inflammatory AT-derived mediator, leptin, prior to virus inoculation, did not alter the expression of endothelial SARS-CoV-2 entry receptors and did not alter their susceptibility to infection. Furthermore, it did not induce inflammatory activation of endothelial cells. To verify if the lack of activated phenotype in the presence of adipokines was not leptin-specific, we exposed endothelial cells to plasma obtained from critically ill obese COVID-19 patients. Plasma exposure did not result in E-selectin, VCAM-1, ICAM-1, or IL-6 induction. Together our results strongly suggest that aberrant inflammatory endothelial responses are not mounted by direct SARS-CoV-2 infection of endothelial cells, even in the presence of leptin and other mediators of obesity. Instead, endothelial activation associated with COVID-19 is likely a result of inflammatory responses initiated by other cells. Further studies are required to investigate the mechanisms regulating endothelial behavior in COVID-19 and the mechanisms driving severe disease in obese individuals.

Levels of Leptin, Adiponectin, and Insulin in COVID-19 Patients

In SARS-CoV-2 infected patients, obesity is a risk factor for the development of respiratory failure. Many pro-inflammatory adipokines and mediators are produced from adipose tissue. Blood samples were collected from 60 COVID-19 patients after three to five days from symptoms and signs were appeared like headache, fatigue, fever, and cough. All patients were diagnosed as positive COVID-19 infection with a pharyngeal swab which is positive by RT-PCR who attended to Isolated Hospital in Tikrit City in Iraq from December 2020 to March 2021 and 30 samples from healthy individuals. Levels of leptin, adiponectin, and insulin were increased in COVID-19 patients with highly significant (P≤0.01) when compared with healthy individuals. Increased levels of leptin, adiponectin, and insulin in COVID-19 patients may occur because all patients were obese with severe respiratory inflammation. © 2022 Medicina Moderna. All rights reserved.

Obesity and Leptin Resistance in the Regulation of the Type I Interferon Early Response and the Increased Risk for Severe COVID-19.

Obesity, and obesity-associated conditions such as hypertension, chronic kidney disease, type 2 diabetes, and cardiovascular disease, are important risk factors for severe Coronavirus disease-2019 (COVID-19). The common denominator is metaflammation, a portmanteau of metabolism and inflammation, which is characterized by chronically elevated levels of leptin and pro-inflammatory cytokines. These induce the "Suppressor Of Cytokine Signaling 1 and 3" (SOCS1/3), which deactivates the leptin receptor and also other SOCS1/3 sensitive cytokine receptors in immune cells, impairing the type I and III interferon early responses. By also upregulating SOCS1/3, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 adds a significant boost to this. The ensuing consequence is a delayed but over-reactive immune response, characterized by high-grade inflammation (e.g., cytokine storm), endothelial damage, and hypercoagulation, thus leading to severe COVID-19. Superimposing an acute disturbance, such as a SARS-CoV-2 infection, on metaflammation severely tests resilience. In the long run, metaflammation causes the "typical western" conditions associated with metabolic syndrome. Severe COVID-19 and other serious infectious diseases can be added to the list of its short-term consequences. Therefore, preventive measures should include not only vaccination and the well-established actions intended to avoid infection, but also dietary and lifestyle interventions aimed at improving body composition and preventing or reversing metaflammation.

Anti-Obesity Effects of Ecklonia cava Extract in High-Fat Diet-Induced Obese Rats.

Obesity is becoming a global epidemic as a result of high-calorie food intake and unhealthy lifestyles. Different marine plants, especially brown algae (Ecklonia cava), are traditionally used to treat different health-related issues. The study was carried out to investigate the anti-obesity properties of E. cava 70% ethanol extract. To evaluate the anti-obesity effect of E. cava, both in vitro and in vivo tests were performed. E. cava suppresses pre-adipocyte 3T3-L1 differentiation in a dose-dependent manner. In HFD-induced obese rats' models, administration of E. cava 125, 250, and 500 mg/kg significantly decreases total body weight and organs, especially liver weight, in all treatment groups. Adipose tissue weight, including subcutaneous, epididymal, peritoneal, and mesenteric adipose tissue, was markedly reduced in E. cava-treated HFD rats in dose-dependent manners. In addition, liver-related biomarkers AST, ALP, ALT, and GGT were evaluated; the lower level of liver-related biomarkers indicates no liver injury or fatty liver issue in E. cava HFD treatment groups. In addition, E. cava treatment has significant effects on the expression of adipogenic and lipogenic (PPAR-γ, FAS, LPL, and SREBP-1c) genes. Altogether, these results show the anti-obesity effect of E. cava. We concluded that E. cava could be a potential candidate for the prevention of obesity-induced by a high-fat diet.

Plasma Leptin Is Increased in Intensive Care Patients with COVID-19-An Investigation Performed in the PronMed-Cohort.

COVID-19 has shaken the world and intensive care units (ICU) have been challenged by numerous patients suffering from a previously unknown disease. Leptin is a polypeptide pleiotropic hormone, mainly expressed by adipocytes. It acts as a proinflammatory cytokine and is associated with several conditions, known to increase the risk of severe COVID-19. Very little is known about leptin in severe viral disorders. Plasma leptin was analyzed in 222 out of 229 patients with severe COVID-19 on admission to an ICU at Uppsala University Hospital, a tertiary care hospital in Sweden, and compared to plasma leptin in 25 healthy blood donors. COVID-19 was confirmed by positive PCR. Leptin levels were significantly higher in patients with COVID-19 (18.3 ng × mL-1; IQR = 30.4), than in healthy controls (7.8 ng × mL-1; IQR = 6.4). Women had significantly higher leptin values (22.9 ng × mL-1; IQR = 29.8) than men (17.5 ng × mL-1; IQR = 29.9). Mortality at 30 days was 23% but was not associated with increased leptin levels. Neither median duration of COVID-19 before admission to ICU (10 days; IQR = 4) or median length of ICU stay (8 days; IQR = 11) correlated with the plasma leptin levels. Leptin levels in COVID-19 were higher in females than in males. Both treatment (e.g., use of corticosteroids) and prophylaxis (vaccines) have been improved since the start of the COVID-19 pandemic, which may contribute to some difficulties in deciphering relations between COVID-19 and leptin.

Obesity and its pharmacological treatments. Future perspectives. Review

WHO details that obesity has reached epidemic proportions worldwide and each year at least 2.8 million people die from obesity or overweight. Disease compromises the different body systems with a life expectancy of between 5 and 20 years approximately. Growing data set suggests that end results related to the disease caused by the SARS-CoV-2 virus are worse in patients who are obese and that a significant proportion of those in intensive care are overweight or obese. The present study aims to systematically review the available evidence regarding obesity, its characteristics, current drug therapy and its future prospects. The information was obtained using scientific databases. The literature review highlights the advances in the development of combined pharmacological therapies for the treatment of obesity beyond interventions in diet or lifestyle. Experimental combination drug therapy includes phentarmine/topiramate and naltrexone/bupropion combinations as well as incretin hormone inhibitors, showing drug combinations such as glucagon-like peptide-1 (GLP-1) with glucose-dependent receptor agonist drugs. insulin-tropic peptides (GIP).