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1.
Biomolecules ; 11(12)2021 12 04.
Article in English | MEDLINE | ID: covidwho-1593561

ABSTRACT

Obesity is a health problem with increasing impacts on public health, economy and even social life. In order to reestablish the energy balance, obesity management focuses mainly on two pillars; exercise and diet. Beyond the contribution to the caloric intake, the diet nutrients and composition govern a variety of properties. This includes the energy balance-independent properties and the indirect metabolic effects. Whereas the energy balance-independent properties are close to "pharmacological" effects and include effects such as antioxidant and anti-inflammatory, the indirect metabolic effects represent the contribution a diet can have on energy metabolism beyond the caloric contribution itself, which include the food intake control and metabolic changes. As an illustration, we also described the metabolic implication and hypothetical pathways of the high-fat diet-induced gene Trefoil Factor Family 2. The properties the diet has can have a variety of applications mainly in pharmacology and nutrition and further explore the "pharmacologically" active food towards potential therapeutic applications.


Subject(s)
Caloric Restriction/methods , Obesity/diet therapy , Trefoil Factor-2/metabolism , Diet, High-Fat/adverse effects , Energy Metabolism/drug effects , Humans , Obesity/metabolism , Up-Regulation/drug effects
2.
Lancet Diabetes Endocrinol ; 9(11): 786-798, 2021 11.
Article in English | MEDLINE | ID: covidwho-1586178

ABSTRACT

Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.


Subject(s)
COVID-19/epidemiology , COVID-19/metabolism , Disease Management , Metabolic Diseases/epidemiology , Metabolic Diseases/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/therapy , Diabetes Mellitus/epidemiology , Diabetes Mellitus/metabolism , Diabetes Mellitus/therapy , Humans , Hypertension/epidemiology , Hypertension/metabolism , Hypertension/therapy , Metabolic Diseases/therapy , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/therapy , Obesity/epidemiology , Obesity/metabolism , Obesity/therapy
3.
Int J Mol Sci ; 23(1)2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1580701

ABSTRACT

Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient's plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ.


Subject(s)
Antiviral Agents/adverse effects , Antiviral Agents/metabolism , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Hydroxychloroquine/metabolism , Aged , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/metabolism , Cell Line , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury/metabolism , Correlation of Data , Drug-Related Side Effects and Adverse Reactions , Fatty Acids/pharmacology , Fatty Liver/complications , Fatty Liver/metabolism , Female , Humans , Hydroxychloroquine/therapeutic use , Linear Models , Male , Metabolic Networks and Pathways , Middle Aged , Obesity/complications , Obesity/metabolism , Risk Factors
4.
Front Immunol ; 12: 732913, 2021.
Article in English | MEDLINE | ID: covidwho-1504188

ABSTRACT

Obesity prevails worldwide to an increasing effect. For example, up to 42% of American adults are considered obese. Obese individuals are prone to a variety of complications of metabolic disorders including diabetes mellitus, hypertension, cardiovascular disease, and chronic kidney disease. Recent meta-analyses of clinical studies in patient cohorts in the ongoing coronavirus-disease 2019 (COVID-19) pandemic indicate that the presence of obesity and relevant disorders is linked to a more severe prognosis of COVID-19. Given the significance of obesity in COVID-19 progression, we provide a review of host metabolic and immune responses in the immunometabolic dysregulation exaggerated by obesity and the viral infection that develops into a severe course of COVID-19. Moreover, sequela studies of individuals 6 months after having COVID-19 show a higher risk of metabolic comorbidities including obesity, diabetes, and kidney disease. These collectively implicate an inter-systemic dimension to understanding the association between obesity and COVID-19 and suggest an interdisciplinary intervention for relief of obesity-COVID-19 complications beyond the phase of acute infection.


Subject(s)
COVID-19/immunology , COVID-19/metabolism , Obesity/immunology , Obesity/metabolism , COVID-19/complications , Disease Progression , Host-Pathogen Interactions/immunology , Humans , Immunity , Metabolic Diseases/immunology , Metabolic Diseases/metabolism , Obesity/complications , Prognosis , SARS-CoV-2/pathogenicity , Severity of Illness Index
5.
Int J Mol Sci ; 22(18)2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1448875

ABSTRACT

The metabolic syndrome (MetS) consists of a cluster of metabolic abnormalities including central obesity, insulin resistance, glucose intolerance, hypertension, and atherogenic dyslipidemia [...].


Subject(s)
Metabolic Syndrome/metabolism , Obesity/metabolism , Animals , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/physiopathology , Humans , Insulin Resistance/physiology , Metabolic Syndrome/physiopathology , Obesity/physiopathology
6.
Cells ; 10(10)2021 10 03.
Article in English | MEDLINE | ID: covidwho-1444118

ABSTRACT

The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals.


Subject(s)
Adipose Tissue, White/metabolism , B7-H1 Antigen/biosynthesis , Gene Expression Regulation , Mesenchymal Stem Cells/cytology , Obesity/metabolism , T-Lymphocytes/immunology , Animals , COVID-19/immunology , Cell Differentiation , Coculture Techniques , Humans , Immunohistochemistry , Inflammation , Interferon-gamma/metabolism , Leukocytes, Mononuclear/cytology , Male , Mice , Mice, Inbred C57BL , Obesity/immunology , SARS-CoV-2 , T-Lymphocytes/cytology
7.
Nutrients ; 13(10)2021 Sep 25.
Article in English | MEDLINE | ID: covidwho-1438684

ABSTRACT

BACKGROUND: Obesity increases the severity of SARS-CoV-2 outcomes. Thus, this study tested whether obesogenic and ketogenic diets distinctly affect SARS-CoV-2 entry proteins and the renin-angiotensin system (RAS) in rat pulmonary and cardiac tissues. METHODS: Male Sprague-Dawley rats were fed either standard chow (SC), a high-fat sucrose-enriched diet (HFS), or a ketogenic diet (KD) for 16 weeks. Afterwards, levels of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), RAS components, and inflammatory genes were measured in the lungs and hearts of these animals. RESULTS: In the lungs, HFS elevated ACE2 and TMPRSS2 levels relative to SC diet, whereas the KD lowered the levels of these proteins and the gene expressions of toll-like receptor 4 and interleukin-6 receptor relative to HFS. The diets did not alter ACE2 and TMPRSS2 in the heart, although ACE2 was more abundant in heart than lung tissues. CONCLUSION: Diet-induced obesity increased the levels of viral entry proteins in the lungs, providing a mechanism whereby SARS-CoV-2 infectivity can be enhanced in obese individuals. Conversely, by maintaining low levels of ACE2 and TMPRSS2 and by exerting an anti-inflammatory effect, the KD can potentially attenuate the severity of infection and migration of SARS-CoV-2 to other ACE2-expressing tissues.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , Diet, High-Fat/adverse effects , Diet, Ketogenic/methods , Lung/metabolism , Myocardium/metabolism , Serine Endopeptidases/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Biomarkers/metabolism , COVID-19/complications , COVID-19/metabolism , Disease Models, Animal , Male , Obesity/complications , Obesity/metabolism , Rats , Rats, Sprague-Dawley , Renin-Angiotensin System , SARS-CoV-2 , Serine Endopeptidases/genetics , Virus Internalization
8.
Horm Metab Res ; 53(9): 575-587, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1397932

ABSTRACT

Global warming and the rising prevalence of obesity are well described challenges of current mankind. Most recently, the COVID-19 pandemic arose as a new challenge. We here attempt to delineate their relationship with each other from our perspective. Global greenhouse gas emissions from the burning of fossil fuels have exponentially increased since 1950. The main contributors to such greenhouse gas emissions are manufacturing and construction, transport, residential, commercial, agriculture, and land use change and forestry, combined with an increasing global population growth from 1 billion in 1800 to 7.8 billion in 2020 along with rising obesity rates since the 1980s. The current Covid-19 pandemic has caused some decline in greenhouse gas emissions by limiting mobility globally via repetitive lockdowns. Following multiple lockdowns, there was further increase in obesity in wealthier populations, malnutrition from hunger in poor populations and death from severe infection with Covid-19 and its virus variants. There is a bidirectional relationship between adiposity and global warming. With rising atmospheric air temperatures, people typically will have less adaptive thermogenesis and become less physically active, while they are producing a higher carbon footprint. To reduce obesity rates, one should be willing to learn more about the environmental impact, how to minimize consumption of energy generating carbon dioxide and other greenhouse gas emissions, and to reduce food waste. Diets lower in meat such as a Mediterranean diet, have been estimated to reduce greenhouse gas emissions by 72%, land use by 58%, and energy consumption by 52%.


Subject(s)
Climate Change , Obesity/etiology , Agriculture/economics , Agriculture/trends , COVID-19/complications , COVID-19/epidemiology , COVID-19/pathology , Climate Change/history , Comorbidity , Endocrine Disruptors/toxicity , Environment , Environmental Exposure/history , Environmental Exposure/statistics & numerical data , Greenhouse Gases/toxicity , History, 19th Century , History, 20th Century , History, 21st Century , Humans , Obesity/epidemiology , Obesity/metabolism , Pandemics , Risk Factors
9.
Front Endocrinol (Lausanne) ; 12: 726967, 2021.
Article in English | MEDLINE | ID: covidwho-1394754

ABSTRACT

In March 2020, the WHO declared coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a global pandemic. Obesity was soon identified as a risk factor for poor prognosis, with an increased risk of intensive care admissions and mechanical ventilation, but also of adverse cardiovascular events. Obesity is associated with adipose tissue, chronic low-grade inflammation, and immune dysregulation with hypertrophy and hyperplasia of adipocytes and overexpression of pro-inflammatory cytokines. However, to implement appropriate therapeutic strategies, exact mechanisms must be clarified. The role of white visceral adipose tissue, increased in individuals with obesity, seems important, as a viral reservoir for SARS-CoV-2 via angiotensin-converting enzyme 2 (ACE2) receptors. After infection of host cells, the activation of pro-inflammatory cytokines creates a setting conducive to the "cytokine storm" and macrophage activation syndrome associated with progression to acute respiratory distress syndrome. In obesity, systemic viral spread, entry, and prolonged viral shedding in already inflamed adipose tissue may spur immune responses and subsequent amplification of a cytokine cascade, causing worse outcomes. More precisely, visceral adipose tissue, more than subcutaneous fat, could predict intensive care admission; and lower density of epicardial adipose tissue (EAT) could be associated with worse outcome. EAT, an ectopic adipose tissue that surrounds the myocardium, could fuel COVID-19-induced cardiac injury and myocarditis, and extensive pneumopathy, by strong expression of inflammatory mediators that could diffuse paracrinally through the vascular wall. The purpose of this review is to ascertain what mechanisms may be involved in unfavorable prognosis among COVID-19 patients with obesity, especially cardiovascular events, emphasizing the harmful role of excess ectopic adipose tissue, particularly EAT.


Subject(s)
COVID-19/metabolism , Cardiomyopathies/metabolism , Intra-Abdominal Fat/metabolism , Obesity/metabolism , Adipose Tissue/metabolism , Adipose Tissue/pathology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/immunology , Cardiomyopathies/immunology , Cardiomyopathies/pathology , Heart Diseases/immunology , Heart Diseases/metabolism , Heart Diseases/pathology , Humans , Inflammation , Intra-Abdominal Fat/pathology , Obesity/complications , Obesity/immunology , Obesity/pathology , Pericardium , Prognosis , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism
10.
Am J Clin Nutr ; 114(5): 1655-1665, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1349771

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) serves protective functions in metabolic, cardiovascular, renal, and pulmonary diseases and is linked to COVID-19 pathology. The correlates of temporal changes in soluble ACE2 (sACE2) remain understudied. OBJECTIVES: We explored the associations of sACE2 with metabolic health and proteome dynamics during a weight loss diet intervention. METHODS: We analyzed 457 healthy individuals (mean ± SD age: 39.8 ± 6.6 y) with BMI 28-40 kg/m2 in the DIETFITS (Diet Intervention Examining the Factors Interacting with Treatment Success) study. Biochemical markers of metabolic health and 236 proteins were measured by Olink CVDII, CVDIII, and Inflammation I arrays at baseline and at 6 mo during the dietary intervention. We determined clinical and routine biochemical correlates of the diet-induced change in sACE2 (ΔsACE2) using stepwise linear regression. We combined feature selection models and multivariable-adjusted linear regression to identify protein dynamics associated with ΔsACE2. RESULTS: sACE2 decreased on average at 6 mo during the diet intervention. Stronger decline in sACE2 during the diet intervention was independently associated with female sex, lower HOMA-IR and LDL cholesterol at baseline, and a stronger decline in HOMA-IR, triglycerides, HDL cholesterol, and fat mass. Participants with decreasing HOMA-IR (OR: 1.97; 95% CI: 1.28, 3.03) and triglycerides (OR: 2.71; 95% CI: 1.72, 4.26) had significantly higher odds for a decrease in sACE2 during the diet intervention than those without (P ≤ 0.0073). Feature selection models linked ΔsACE2 to changes in α-1-microglobulin/bikunin precursor, E-selectin, hydroxyacid oxidase 1, kidney injury molecule 1, tyrosine-protein kinase Mer, placental growth factor, thrombomodulin, and TNF receptor superfamily member 10B. ΔsACE2 remained associated with these protein changes in multivariable-adjusted linear regression. CONCLUSIONS: Decrease in sACE2 during a weight loss diet intervention was associated with improvements in metabolic health, fat mass, and markers of angiotensin peptide metabolism, hepatic and vascular injury, renal function, chronic inflammation, and oxidative stress. Our findings may improve the risk stratification, prevention, and management of cardiometabolic complications.This trial was registered at clinicaltrials.gov as NCT01826591.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Body Composition , COVID-19/metabolism , Diet, Reducing , Obesity/metabolism , Proteome/metabolism , Weight Loss/physiology , Adipose Tissue/metabolism , Adult , Biomarkers/blood , Body Mass Index , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Humans , Inflammation , Insulin Resistance , Male , Middle Aged , Obesity/diet therapy , Oxidative Stress , Pandemics , SARS-CoV-2 , Triglycerides/blood , Weight Reduction Programs
11.
Int J Mol Sci ; 22(15)2021 Jul 31.
Article in English | MEDLINE | ID: covidwho-1346501

ABSTRACT

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1α expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFκB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.


Subject(s)
Anti-Obesity Agents/therapeutic use , Arachidonic Acids/therapeutic use , Benzoates/therapeutic use , Obesity/drug therapy , Phenylurea Compounds/therapeutic use , Adipogenesis , Adipose Tissue, Brown/cytology , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/metabolism , Animals , Anti-Obesity Agents/administration & dosage , Anti-Obesity Agents/pharmacology , Arachidonic Acids/administration & dosage , Arachidonic Acids/pharmacology , Benzoates/administration & dosage , Benzoates/pharmacology , Blood Glucose/metabolism , Carnitine O-Palmitoyltransferase/metabolism , Diet, High-Fat , Epoxide Hydrolases/antagonists & inhibitors , Fatty Acids/metabolism , Male , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Obesity/etiology , Obesity/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/pharmacology
12.
Biochimie ; 179: 257-265, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1326917

ABSTRACT

It is becoming obvious that in addition to aging and various hearth pathologies, excess of body weight, especially obesity is a major risk factor for severity of COVID-19 infection. Intriguingly the receptor for SARS-CoV-2 is ACE2, a member of the angiotensin receptor family that has a relatively large tissue distribution. This observation likely explains the multitude of symptoms that have been described from human patients. The adipose tissue also expresses ACE2, suggesting that adipocytes are potentially infected by SARS-CoV-2. Here we discuss some of the potential contribution of the adipose tissue to the severity of the infection and propose some aspects of obese patients metabolic phenotyping to help stratification of individuals with high risk of severe disease.


Subject(s)
COVID-19/complications , Obesity/complications , Adipose Tissue/pathology , Adipose Tissue/virology , Cytokines/metabolism , Humans , Obesity/metabolism , Obesity/pathology , Prevalence
13.
Int J Mol Sci ; 22(15)2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1325686

ABSTRACT

The present review is aimed at analysing the current evidence concerning the potential modulation of obesity and/or diet in adipose tissue ACE2. Additionally, the potential implications of these effects on COVID-19 are also addressed. The results published show that diet and obesity are two factors that effectively influence the expression of Ace2 gene in adipose tissue. However, the shifts in this gene do not always occur in the same direction, nor with the same intensity. Additionally, there is no consensus regarding the implications of increased adipose tissue ACE2 expression in health. Thus, while in some studies a protective role is attributed to ACE2 overexpression, other studies suggest otherwise. Similarly, there is much debate regarding the role played by ACE2 in COVID-19 in terms of degree of infection and disease outcomes. The greater risk of infection that may hypothetically derive from enhanced ACE2 expression is not clear since the functionality of the enzyme seems to be as important as the abundance. Thus, the greater abundance of ACE2 in adipose tissue of obese subjects may be counterbalanced by its lower activation. In addition, a protective role of ACE2 overexpression has also been suggested, associated with the increase in anti-inflammatory factors that it may produce.


Subject(s)
Adipose Tissue/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Obesity/metabolism , Angiotensin-Converting Enzyme 2/genetics , Animals , Diet , Humans , Renin-Angiotensin System/physiology , Severity of Illness Index
14.
J Endocrinol ; 249(1): 57-70, 2021 04.
Article in English | MEDLINE | ID: covidwho-1314460

ABSTRACT

Vaspin is a novel adipokine mainly expressed in visceral adipose tissue and closely related to obesity and insulin-resistance. Currently, data about its ovarian expression are limited to animal models and its role in human reproduction is largely unexplored. Our study's aims were then to characterise vaspin expression in the human ovary and to study in vitro its effects on granulosa cells physiology. Secondly, we assessed vaspin and its receptor GRP78 variations in granulosa cells and follicular fluid of a cohort of 112 infertile women undergoing an in vitro fertilisation procedure and allocated to three groups, each including normal-weight and obese subjects: 34 PCOS patients, 33 women with isolated polycystic ovary morphology (ECHO group) and 45 controls. Vaspin and GRP78 expression in the ovary was assessed by immunohistochemistry, RT-qPCR and Western blot. Granulosa cells and follicular fluid were analysed by RT-qPCR and ELISA, respectively. In vitro, granulosa cells metabolism was studied after stimulation with recombinant human vaspin, with and without a siRNA directed against GRP78. Vaspin was highly expressed in the human ovary and concentration-dependently enhanced granulosa cells steroidogenesis, proliferation and viability through GRP78 (P < 0.0001). Vaspin levels in both granulosa cells and follicular fluid were significantly higher in obese women (P < 0.0001) and in the normal-weight ECHO group (P < 0.001), which also had the highest expression rates of GRP78 (P < 0.05). Although further investigation is needed, vaspin appears as a novel modulator of human granulosa cells physiology and possibly plays a role in PCOS pathogenesis, notably protecting from insulin-resistance induced complications.


Subject(s)
Granulosa Cells/physiology , Heat-Shock Proteins/physiology , Polycystic Ovary Syndrome/physiopathology , Serpins/physiology , Adult , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Fertilization in Vitro , Follicular Fluid/chemistry , France , Gene Expression , Granulosa Cells/chemistry , Granulosa Cells/drug effects , Heat-Shock Proteins/analysis , Heat-Shock Proteins/genetics , Humans , Infertility, Female/therapy , Insulin Resistance/physiology , Obesity/metabolism , Ovary/chemistry , Ovary/metabolism , RNA, Messenger/analysis , Serpins/genetics , Serpins/pharmacology , Steroids/biosynthesis
15.
Obes Rev ; 22(10): e13313, 2021 10.
Article in English | MEDLINE | ID: covidwho-1314091

ABSTRACT

Coronaviruses are constantly circulating in humans, causing common colds and mild respiratory infections. In contrast, infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease-2019 (COVID-19), can cause additional severe complications, particularly in patients with obesity and associated metabolic disturbances. Obesity is a principal causative factor in the development of the metabolic syndrome; a series of physiological, biochemical, clinical, and metabolic factors that increase the risk of obesity-associated diseases. "Metabolically unhealthy" obesity is, in addition to metabolic disturbances, also associated with immunological disturbances. As such, patients with obesity are more prone to develop serious complications from infections, including those from SARS-CoV-2. In this review, we first describe how obesity and related metabolic disturbances increase the risk of SARS-CoV-2 infection. Then, mechanisms contributing to COVID-19 complications and poor prognosis in these patients are discussed. Finally, we discuss how obesity potentially reduces long-term COVID-19 vaccination efficacy. Despite encouraging COVID-19 vaccination results in patients with obesity and related metabolic disturbances in the short-term, it is becoming increasingly evident that long-term COVID-19 vaccination efficacy should be closely monitored in this vulnerable group.


Subject(s)
COVID-19 Vaccines , COVID-19 , Disease Progression , Obesity/complications , Obesity/metabolism , COVID-19/complications , COVID-19/immunology , COVID-19/physiopathology , COVID-19/prevention & control , Humans , SARS-CoV-2 , Vaccination
16.
Cardiol Rev ; 29(6): 292-295, 2021.
Article in English | MEDLINE | ID: covidwho-1310959

ABSTRACT

The coronavirus 2019 (COVID-19) pandemic has presented many new challenges to the healthcare community with the sheer number of individuals affected and the range of symptoms at presentation. Early findings have shown that increased age is an independent risk factor for COVID-19 severity. Diabetes and hypertension were also found to be strong independent risk factors for severe COVID-19. It was later discovered that obesity is a strong risk factor for severe disease as well. Possible mechanisms for the increased risk associated with metabolic disease include the increased prevalence of acute respiratory syndrome, immune cell dysfunction, and chronic inflammatory states associated with obesity and diabetes. Acknowledging these risk factors has consequences for addressing vaccination strategies as well as healthcare disparities.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus/epidemiology , Hypertension/epidemiology , Obesity/epidemiology , COVID-19/metabolism , COVID-19/mortality , COVID-19/physiopathology , Comorbidity , Diabetes Mellitus/metabolism , Diabetes Mellitus/physiopathology , Humans , Hypertension/metabolism , Hypertension/physiopathology , Inflammation/metabolism , Obesity/metabolism , Obesity/physiopathology , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/physiopathology , Risk Factors , SARS-CoV-2 , Severity of Illness Index
17.
Int J Mol Sci ; 22(13)2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1295858

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has claimed over 2.7 million lives globally. Obesity has been associated with increased severity and mortality of COVID-19. However, the molecular mechanisms by which obesity exacerbates COVID-19 pathologies are not well-defined. The levels of free fatty acids (FFAs) are elevated in obese subjects. This study was therefore designed to examine how excess levels of different FFAs may affect the progression of COVID-19. Biological molecules associated with palmitic acid (PA) and COVID-19 were retrieved from QIAGEN Knowledge Base, and Ingenuity Pathway Analysis tools were used to analyze these datasets and explore the potential pathways affected by different FFAs. Our study found that one of the top 10 canonical pathways affected by PA was the coronavirus pathogenesis pathway, mediated by key inflammatory mediators, including PTGS2; cytokines, including IL1ß and IL6; chemokines, including CCL2 and CCL5; transcription factors, including NFκB; translation regulators, including EEF1A1; and apoptotic mediators, including BAX. In contrast, n-3 fatty acids may attenuate PA's activation of the coronavirus pathogenesis pathway by inhibiting the activity of such mediators as IL1ß, CCL2, PTGS2, and BAX. Furthermore, PA may modulate the expression of ACE2, the main cell surface receptor for the SARS-CoV-2 spike protein.


Subject(s)
COVID-19/metabolism , Fatty Acids, Nonesterified/metabolism , Obesity/metabolism , Palmitic Acid/metabolism , SARS-CoV-2/pathogenicity , COVID-19/blood , COVID-19/epidemiology , COVID-19/pathology , Chemokines/metabolism , Computational Biology/methods , Cytokines/metabolism , Databases, Factual , Fatty Acids, Nonesterified/blood , Humans , Inflammation Mediators/metabolism , Obesity/pathology , Pandemics , SARS-CoV-2/isolation & purification
18.
Inflammopharmacology ; 29(4): 1017-1031, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1286160

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-COV-2) is the culprit of the Coronavirus Disease (COVID-19), which has infected approximately 173 million people and killed more than 3.73 million. At risk groups including diabetic and obese patients are more vulnerable to COVID-19-related complications and poor outcomes. Substantial evidence points to hypovitaminosis D as a risk factor for severe disease, the need for ICU, and mortality. 1,25(OH)D, a key regulator of calcium homeostasis, is believed to have various immune-regulatory roles including; promoting anti-inflammatory cytokines, down regulating pro-inflammatory cytokines, dampening entry and replication of SARS-COV-2, and the production of antimicrobial peptides. In addition, there are strong connections which suggest that dysregulated 1,25(OH)D levels play a mechanistic and pathophysiologic role in several disease processes that are shared with COVID-19 including: diabetes, obesity, acute respiratory distress syndrome (ARDS), cytokine storm, and even hypercoagulable states. With evidence continuing to grow for the case that low vitamin D status is a risk factor for COVID-19 disease and poor outcomes, there is a need now to address the public health efforts set in place to minimize infection, such as lock down orders, which may have inadvertently increased hypovitaminosis D in the general population and those already at risk (elderly, obese, and disabled). Moreover, there is a need to address the implications of this evidence and how we may apply the use of cheaply available supplementation, which has yet to overcome the near global concern of hypovitaminosis D. In our review, we exhaustively scope these shared pathophysiologic connections between COVID-19 and hypovitaminosis D.


Subject(s)
COVID-19/metabolism , Cytokine Release Syndrome/metabolism , Thrombophilia/metabolism , Vitamin D Deficiency/metabolism , Vitamin D/administration & dosage , Vitamin D/metabolism , COVID-19/complications , COVID-19/drug therapy , COVID-19/physiopathology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/physiopathology , Humans , Obesity/epidemiology , Obesity/metabolism , Obesity/physiopathology , Risk Factors , Thrombophilia/drug therapy , Thrombophilia/physiopathology , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/physiopathology
19.
Sci Rep ; 11(1): 8712, 2021 04 22.
Article in English | MEDLINE | ID: covidwho-1253973

ABSTRACT

Obesity is associated with both chronic and acute respiratory illnesses, such as asthma, chronic obstructive pulmonary disease (COPD) or increased susceptibility to infectious diseases. Anatomical but also systemic and local metabolic alterations are proposed contributors to the pathophysiology of lung diseases in the context of obesity. To bring perspective to this discussion, we used NMR to compare the obesity-associated metabolomic profiles of the lung with those of the liver, heart, skeletal muscles, kidneys, brain and serum from male C57Bl/6J mice fed with a high-fat and high-sucrose (HFHSD) diet vs. standard (SD) chow for 14 weeks. Our results showed that the lung was the second most affected organ after the liver, and that the two organs shared reduced one-carbon (1C) metabolism and increased lipid accumulation. Altered 1C metabolism was found in all organs and in the serum, but serine levels were increased only in the lung of HFHSD compared to SD. Lastly, tricarboxylic acid (TCA)-derived metabolites were specifically and oppositely regulated in the serum and kidneys but not in other organs. Collectively, our data highlighted that HFHSD induced specific metabolic changes in all organs, the lung being the second most affected organ, the main alterations affecting metabolite concentrations of the 1C pathway and, to a minor extend, TCA. The absolute metabolite quantification performed in this study reveals some metabolic specificities affecting both the liver and the lung, that may reveal common metabolic determinants to the ongoing pathological process.


Subject(s)
Diet, High-Fat , Dietary Sucrose/administration & dosage , Lipid Metabolism , Liver/metabolism , Lung/metabolism , Obesity/metabolism , Animals , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred BALB C
20.
Eur J Clin Invest ; 51(7): e13597, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1242159

ABSTRACT

BACKGROUND: Social containment measures imposed in Europe during the lockdown to face COVID-19 pandemic can generate long-term potential threats for metabolic health. METHODS: A cohort of 494 non-COVID-19 subjects living in 21 EU countries were interviewed by an anonymous questionnaire exploring anthropometric and lifestyle changes during 1-month lockdown. A subgroup of 41 overweight/obese Italian subjects with previously diagnosed nonalcoholic fatty liver (NAFLD) joined the study following a 12-month follow-up period promoting weight loss by healthy lifestyle. RESULTS: During the lockdown, body weight increased in 55% of subjects (average 2.4 ± 0.9 kg). Weight change increased with age, but not baseline body mass index. Subjects living in Italy had greater weight gain than those living in other European Countries. Weight gain during the lockdown was highest in subjects reporting no physical activity, and low adherence to Mediterranean diet. In the NAFLD group, weight gain occurred in 70% of cases. Subjects reporting weight loss during lockdown had decreased fatty liver score at 3 months before the lockdown, as compared with 1 year before. CONCLUSIONS: Strict measures of social containment-even short-term-pave the way to the increased risk of metabolic abnormalities in the medium-long term. In this context, adherence to Mediterranean diet and regular physical activity play a protective role both in terms of weight gain and fatty liver development/progression, with implication for primary and secondary prevention. When adopting measures imposing social containment, intensive educational campaigns must increase public awareness about beneficial effects of healthy lifestyles.


Subject(s)
COVID-19 , Diet/statistics & numerical data , Exercise , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Obesity/metabolism , Weight Gain , Adolescent , Adult , Communicable Disease Control , Diet, Mediterranean , European Union , Female , Humans , Italy , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/metabolism , Overweight/metabolism , Public Policy , SARS-CoV-2 , Surveys and Questionnaires , Young Adult
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