Systemic Inflammation In Obesity Research Articles

The role of the gastrointestinal barrier in obesity-associated systemic inflammation.

Systemic inflammation is a key contributor to the onset and progression of several obesity-associated diseases and is thought to predominantly arise from the hyperplasia and hypertrophy of white adipose tissue. However, a growing body of works suggests that early changes in the gastrointestinal (GI) barrier may contribute to both local, within the GI lining, and systemic inflammation in obesity. Intestinal barrier dysfunction is well-characterized in inflammatory GI disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and is known to contribute to systemic inflammation. Thus, drawing parallels between GI disorders, where intestinal permeability and systemic inflammation are prominent features, and obesity-induced GI manifestations may provide insights into the potential role of the intestinal barrier in systemic inflammation in obesity. This review summarizes the current literature surrounding intestinal barrier dysfunction in obesity and explores the potential role of intestinal hyperpermeability and intestinal barrier dysfunction in the development of systemic inflammation and GI dysfunction in obesity.

FRI076 Colchicine Treatment Effects On The Gut Microbiome In Adults With Metabolic Syndrome, Insulin Resistance, And High C-reactive Protein (CRP): A Secondary Analysis Of A Randomized, Placebo-controlled Clinical Trial

Abstract Disclosure: C.M. Kisimba: None. J.L. Donahue: None. K.K. Chivukula: None. P. Subramanian: None. S.D. Mistry: None. A. Wolska: None. A.T. Remaley: None. J.A. Yanovski: None. A.P. Demidowich: None. Background: Obesity-induced inflammation plays a substantial role in the development of insulin resistance and type 2 diabetes. The altered gut flora in obesity can also contribute to metabolic dysregulation and systemic inflammation. However, it remains unclear how dysregulation of systemic inflammation in obesity affects the gut microbiome. We hypothesized that colchicine’s systemic anti-inflammatory effects in obesity would be associated with improvements in gut microbial diversity. Methods: This study was a secondary analysis of a double-blind randomized placebo-controlled trial, in which 40 adults with obesity, high CRP (≥ 2.0 mg/L), insulin resistance (HOMA-IR ≥ 2.6 mg/L), and metabolic syndrome (MetS) were randomized to three months of colchicine 0.6mg or placebo tablets twice daily. Serum and stool samples were collected at baseline and final visit. Gut microbiota composition was characterized from stool DNA by dual-index amplification and sequencing of 16S ribosomal RNA. Results: Pre- and post-intervention stool samples were available for 15 colchicine- and 12 placebo-treated subjects. Circulating hsCRP, interleukin-6, resistin, white blood count, and neutrophils were significantly decreased in the colchicine arm as compared to placebo. However, changes in stool microbiome alpha diversity, as assessed by the Chao1, Shannon, and Pielou indices, were not significant between groups. Sequence variant counts were unchanged among all examined phyla or families. Oscillibacter was the only genus to demonstrate even a nominally significant change. Conclusion: Among adults with obesity and MetS, colchicine significantly improved systemic inflammation. However, this anti-inflammatory effect was not associated with significant changes in the gut microbiome. Further studies are warranted to investigate this relationship. Presentation: Friday, June 16, 2023

Investigation of the Possible Relation of Apelin, Kynurenine and IL-4/IL-10/IL-12/Tnf-alfa Levels with Clinical and Metabolic Parameters in Obesity

Purpose
 Obesity is a medical condition caused by excess body fat that accumulates at a level that can have a negative impact on health. Altered glucose and lipid metabolism, low-grade chronic inflammation play a role in the pathogenesis of obesity and obesity-related metabolic dysfunction. In our study, we aimed to determine the apelin, kynurenine, IL-4/IL-10/IL-12/TNF-α protein levels in obese individuals and healthy control groups, and to investigate the possible relationship between clinical parameters with the data to be obtained. 
 Materials and Methods
 The levels of Apelin, Kynurenine, IL-4/IL-10/IL-12/TNF-α in serum/plasma samples were measured with enzyme-linked immunosorbent assay. Absorbance of the samples were measured on a microplate reader spectrophotometrically at a wavelength of 450 nm.
 Results
 The levels of Kinurenin, IL-4, and IL-12 in the serum were higher in control group than in obese patients (p=0.009, p=0.004, p=0.002, respectively). There was no significant difference between the control and obese patients in TNF-α, IL-10 and Apelin levels (p=0.277, p=0.711, p=0.472, respectively).
 Conclusion
 Inflammation and altered immune response are two important components of obesity. They play a major role in the formation of metabolic diseases associated with obesity. Changes in adipokine levels may lead to the development and maintenance of insulin resistance and systemic inflammation in obesity. The results demonstrate that kynurenine, IL-4, and IL-12 have a complex role in obesity and can be used as therapeutic targets.

Colchicine effects on the gut microbiome in adults with metabolic syndrome.

Obesity-induced inflammation plays a substantial role in the development of insulin resistance and type 2 diabetes. The altered gut flora in obesity can also contribute to metabolic dysregulation and systemic inflammation. However, it remains unclear how dysregulation of systemic inflammation in obesity affects the gut microbiome. We hypothesized that colchicine's systemic anti-inflammatory effects in obesity would be associated with improvements in gut microbial diversity. We conducted a secondary analysis of a double-blind randomized placebo-controlled trial, in which 40 adults with obesity, high C-reactive protein (CRP) (≥2.0 mg/L), insulin resistance (homeostatic model of insulin resistance: HOMA-IR ≥2.6 mg/L), and metabolic syndrome (MetS) were randomized to three months of colchicine 0.6 mg or placebo tablets twice daily. Serum and stool samples were collected at baseline and final visit. Gut microbiota composition was characterized from stool DNA by dual-index amplification and sequencing of 16S ribosomal RNA. Pre- and post-intervention stool samples were available for 15 colchicine- and 12 placebo-treated subjects. Circulating high sensitivity CRP (hsCRP), interleukin-6, resistin, white blood count, and neutrophils were significantly decreased in the colchicine arm as compared to placebo. However, changes in stool microbiome alpha diversity, as assessed by the Chao1, Shannon, and Pielou indices, were not significant between groups. Amplicon sequence variant counts were unchanged among all examined phyla or families. Oscillibacter was the only genus to demonstrate even a nominally significant change. Among adults with obesity and MetS, colchicine significantly improved systemic inflammation. However, this anti-inflammatory effect was not associated with significant changes in the gut microbiome. Further studies are warranted to investigate this relationship.

Impact of Obesity on Bone Metabolism in Children.

Obesity is an epidemic disease that can increase the incidence of type 2 diabetes, cardiovascular disease, malignancy, hypertension, and other health problems that affect the musculoskeletal system. There is a complex interaction between obesity and bone metabolism. In children with obesity, the peroxisome proliferator-activated receptor gamma pathway causes the differentiation of mesenchymal stem cells into adipocytes via osteoblasts, in which results in low bone mass and osteoporosis. Systemic inflammation in obesity has negative effects on bone metabolism. An increase in the number and size of adipose tissue and adipocytokines secreted from adipocytes affect the bone mass of the whole body with hormonal and biochemical effects. The skeletal effects of obesity are mediated by higher oxidative stress and increased production of proinflammatory cytokines. Osteoporosis due to obesity has increased morbidity and mortality in recent years, resulting in important health problems in developed and developing countries.

Sulforaphane reduces pro-inflammatory response to palmitic acid in monocytes and adipose tissue macrophages

Chronic low-grade systemic inflammation (SI), including activation of the NLRP3 inflammasome, is a feature of obesity, associated with increased circulating saturated fatty acids, such as palmitic acid (PA), and bacterial endotoxin lipopolysaccharide (LPS). PA and LPS may contribute to SI observed in obesity, while the dietary antioxidant sulforaphane has been shown to reduce activation of the NLRP3 inflammasome. This study investigated immune cell responses from obese subjects to PA, and the effects of sulforaphane on NLRP3 activation/inflammation. Peripheral blood monocytes isolated from obese (n = 8) and non-obese (n = 8) subjects and adipose tissue macrophages (ATMs) isolated from visceral fat obtained from obese subjects (n = 10) during bariatric surgery were pre-treated with/without sulforaphane (40 µM) for 3 hours then stimulated with PA (500 µM) ± LPS (1 ng/mL monocytes; 100 ng/mL ATMs) for 15 hours. Culture supernatants were assessed for tumor necrosis factor-α and interleukin-β (IL-1β) by enzyme-linked immunosorbent assay, NLRP3 inflammasome gene expression was assessed by quantitative polymerase chain reaction, IL-1β and NLRP3 expression were higher in both unstimulated and PA treated monocytes from obese compared to nonobese subjects. In ATMs neither PA alone or combined with LPS increased cytokine production or inflammasome gene expression. Sulforaphane reduced tumor necrosis factor-α and IL-1β from monocytes in both groups, however inflammasome associated genes were only reduced in monocytes from obese subjects. Sulforaphane reduced cytokine production and inflammasome gene expression in ATMs. NLRP3 inflammasome activation by PA is higher in obesity, which maybe driven by baseline activation of the NLRP3 inflammasome. Sulforaphane modulates inflammatory responses in immune cells and may play a role in reducing SI in obesity.

Weight Loss and Short-Chain Fatty Acids Reduce Systemic Inflammation in Monocytes and Adipose Tissue Macrophages from Obese Subjects.

Background: Chronic low-grade systemic inflammation is a characteristic of obesity that leads to various non-communicable diseases. Weight loss and SCFAs are potential strategies for attenuating obese systemic inflammation. Methods: Blood samples were collected from 43 obese subjects (BMI ≥ 30 kg/m2) scheduled for laparoscopic bariatric sleeve surgery, 26 obese subjects at follow-up 12–18 months post-surgery and 8 healthy weight subjects (BMI 18.5–24.9 kg/m2). Monocytes were isolated from blood and adipose tissue macrophages from visceral adipose tissue of obese subjects only. Isolated cells stimulated with 1 ng/mL LPS and treated simultaneously with 300 mM of sodium acetate or 30 mM of sodium propionate or butyrate and supernatant were harvested after 15 h incubation. TNF-α and IL-6 cytokines were measured via ELISA and mRNA gene expression of FFAR2 and FFAR3, HDAC1, HDAC2 and HDAC9, RELA and NFKB1 and MAPK1 via RT-qPCR. Results: TNF-α and IL-6 production and NFKB1 and RELA mRNA expression were significantly decreased in follow-up subjects compared to baseline. SCFAs significantly reduced TNF-α and IL-6 and altered FFAR and HDAC mRNA expression in monocytes and macrophages from obese subjects. Conclusion: Weight loss and ex vivo SCFA treatments were successful in combatting systemic inflammation in obesity. Results highlighted molecular changes that occur with weight loss and as a result of SCFA treatment.

Evaluation of Inflammatory Hematological Ratios (NLR, PLR, MLR and Monocyte/HDL-Cholesterol Ratio) in Obese Adolescents

Introduction: Obesity is a gradually more important multifactorial disease in both children and adults. Obese children and adolescents are at higher risk of becoming obese in adulthood, which is associated with an increased risk of mortality and morbidity. There is subclinical systemic inflammation in obesity. The study aimed to evaluate the hematological parameters as an indicator of inflammation in obese adolescents and to show the relationship of monocyte/HDL-cholesterol ratio, having a lipid component, with other inflammatory hematological parameters. Materials and methods: We retrospectively reviewed the medical files of 60 patients, 30 obese and 30 healthy controls, aged between 11 and 16 years, who applied to the pediatric outpatient clinic. Laboratory tests, hematological parameters, gender, age, and BMI were compared between the groups. Correlations between monocyte/HDL-cholesterol ratio and other laboratory parameters in the obese group were examined. Results: BMI, Alanine aminotransferase (ALT), C-reactive protein (CRP), triglyceride, insulin, and HOMA-IR levels of the obese adolescent group were statistically significantly higher than the control group (p<0.05). There was no statistically significant difference between the obese and control groups in terms of inflammatory hematological ratios (NLR, PLR, MLR, and monocyte/HDL-cholesterol ratio) (p>0.05). There was no statistically significant relationship between monocyte/HDL-cholesterol and other inflammatory hematological rates (p>0.05). There was a positive, moderate (48.6%), and statistically significant relationship between monocyte/HDL-cholesterol and MLR (p<0.05). Conclusions: In our study, the NLR, PLR, MLR, and monocyte/HDL-cholesterol values of the obese adolescent group were similar to the control group. There was correlation between monocyte/HDL-cholesterol and monocyte/lymphocyte values. There was no correlation between other rates. Our data do not support the utility of inflammatory hematological rates as a biomarker in adolescent obesity. However, we believe that our study can shed light on other studies to be conducted.

Short-chain fatty acids as anti-inflammatory agents in overweight and obesity: a systematic review and meta-analysis.

Short-chain fatty acids (SCFAs) derived from microbial fermentation of prebiotic soluble fibers are noted for their anti-inflammatory benefits against obese systemic inflammation. A systematic review and meta-analysis were undertaken to investigate the effect of SCFAs and prebiotic interventions on systemic inflammation in obesity. Relevant studies from 1947 to August 2019 were collected from the Cumulative Index to Nursing and Allied Health Literature, Embase, Medline, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Of 61 included studies, 29 were of humans and 32 of animals. Methodological quality of studies was assessed using the critical appraisal checklist of the Academy of Nutrition and Dietetics. Data pertaining to population, intervention type and duration, and markers of systemic inflammation were extracted from included studies. Of 29 included human studies, 3 of 4 SCFA interventions and 11 of 25 prebiotic interventions resulted in a significant decrease in ≥1 biomarker of systemic inflammation. Of 32 included animal studies, 10 of 11 SCFA interventions and 18 of 21 prebiotic interventions resulted in a significant reduction of ≥1 biomarker of systemic inflammation. Meta-analysis revealed that prebiotics in humans reduced levels of plasma high-sensitivity C-reactive protein (standard mean difference [SMD], -0.83; 95%CI: -1.56 to -0.11; I2: 86%; P = 0.02) and plasma lipopolysaccharide (SMD, -1.20; 95%CI: -1.89 to -0.51; I2: 87%; P = 0.0006), and reduced TNF-α levels in animals (SMD, -0.63; 95%CI: -1.19 to -0.07; P = 0.03). Heterogeneity among supplement types, duration, and dose across studies was significant. Evidence from this review and meta-analysis supports the use of SCFAs and prebiotics as novel aids in treatment of obese systemic inflammation. PROSPERO registration no. CRD42020148529.

Effects of Obesity-Associated Chronic Inflammation on Peripheral Blood Immunophenotype Are Not Mediated by TNF in Female C57BL/6J Mice.

Chronic low-grade systemic inflammation in obesity contributes to the development and progression of aspects of metabolic syndrome. In obese male mice, expanded adipose tissue releases proinflammatory cytokines, including TNF, which promotes an increase in immature, proinflammatory, peripheral blood Ly-6Chigh monocytes. The aim of this study was to characterize how TNF alters circulating cellular immunity in female mice with diet-induced obesity. We initially quantified peripheral blood immune cells by flow cytometry in female wild-type C57BL/6J mice after 3-30 wk of allocation to a high-fat (HF) or standard chow diet. We assessed effects of diet and time on neutrophil, monocyte, B cell, NK cell, CD4+ T cell, and CD8+ T cell populations. There was a significant interaction of the effects of diet type and time on the numbers and prevalence of circulating total monocytes and Ly-6Chigh, Ly-6Clow, and Ly-6C- subsets. Circulating monocytes, in particular Ly-6Chigh monocytes, were increased in HF-fed mice compared with chow-fed mice. Ly-6Chigh monocytes from HF-fed mice also had a more immature phenotype yet were highly responsive to the chemotactic ligand CCL2 and had greater intracellular production of TNF. Comparisons of the effects of HF diet feeding in littermate wild-type (TNF+/+) and TNF-/- female mice showed that genetic ablation of TNF did not protect from higher adiposity or an increase in circulating, immature, proinflammatory Ly-6Chigh monocytes during HF diet-induced obesity. These data emphasize the importance of considering biological sex when determining the mechanisms of TNF action in obesity-induced cellular inflammation and in other chronic inflammatory conditions.

DHT Differentially Regulates T Helper Cell Related Cytokines and MicroRNAs In Visceral and Subcutaneous Adipose Tissue of Female Mice

Hyperandrogenemic, insulin resistant polycystic ovarian syndrome (PCOS) patients often have low-grade inflammation due to elevated circulating pro-inflammatory markers. As up to 60% of PCOS patients are obese, whether this low-grade inflammatory state is due to increased adiposity or other factors such as hyperandrogenemia is unknown. Moreover, the systemic inflammation of obesity is correlated with recruitment of pro-inflammatory immune cell populations to WAT. We hypothesized that short-term administration of the potent androgen, dihydrotestosterone (DHT), to female mice would increase pro-inflammatory cytokines and microRNA (miR) associated with pro-inflammatory cytokines and immune cell populations in WAT. Sexually mature, normally-cycling female C57/Bl6 mice received a daily sc injection of oil (0 g; n=7) or DHT (27.5 g; n=7) beginning at estrus. Females had vaginal cytology daily. After three cycles or 12-16 days if mice became acyclic, mice were euthanized for collection of blood and WAT. Serum was analyzed for DHT and testosterone (TEST) by LC-MS/MS. TaqManTM Array Mouse Immune Response PCR assays (Thermofisher Scientific) were used to measure transcript expression levels in vWAT and scWAT. Ingenuity Pathway Analysis (IPA) (Qiagen) was used to analyze relationships between different transcript levels in each treatment group for each tissue. DHT mice had 17 fold higher serum DHT levels than oil mice but there was no difference in serum TEST between treatment groups. DHT mice had a significantly longer estrous cycle length then oil mice. Short-term administration of DHT significantly upregulated 23% (21 of 92) of transcripts in scWAT and downregulated 49% (45 of 92) of transcripts in vWAT. The top four canonical pathways identified by IPA in WAT were: T helper cell 1 (Th1), Th1 & T helper 2 activation, Helper T cell differentiation, and Altered B & T cell signaling. Based on the Th1 pathway derived from IPA, the following miRs (both -3p and 5p) downstream of Th1 activation targets were selected for qPCR in vWAT and scWAT: miR21, miR146a, miR29a, and miR155. Interestingly, miR-21a-5p, miR-146a-5p, and miR-155-5p were significantly upregulated in scWAT from DHT mice. No miRs were different between treatment groups in vWAT. We demonstrate for the first time that short-term DHT administration may cause immunosuppression in vWAT and inflammation, possibly mediated by miRs, in scWAT of female mice.

Risk of Iron Overload in Obesity and Implications in Metabolic Health.

Excessive adiposity is associated with several metabolic perturbations including disturbances in iron homeostasis. Increased systemic inflammation in obesity stimulates expression of the iron regulatory hormone hepcidin, which can result in a maldistribution of bodily iron, which may be implicated in metabolic dysfunction. This study aimed to investigate the effect of adiposity and any associated inflammation on iron homeostasis and the potential implications of dysregulated iron metabolism on metabolic health. Analyses are based on a subsample from the cross-sectional Irish National Adult Nutrition Survey (2008–2010) (n = 1120). Ferritin status and risk of iron overload were determined based on established WHO ferritin ranges. Participants were classed as having a healthy % body fat or as having overfat or obesity based on age- and gender-specific % body fat ranges as determined by bioelectrical impedance. Biomarkers of iron status were examined in association with measures of body composition, serum adipocytokines and markers of metabolic health. Excessive % body fat was significantly associated with increased serum hepcidin and ferritin and an increased prevalence of severe risk of iron overload amongst males independent of dietary iron intake. Elevated serum ferritin displayed significant positive associations with serum triglycerides and markers of glucose metabolism, with an increased but non-significant presentation of metabolic risk factors amongst participants with overfat and obesity at severe risk of iron overload. Increased adiposity is associated with dysregulations in iron homeostasis, presenting as increased serum hepcidin, elevated serum ferritin and an increased risk of iron overload, with potential implications in impairments in metabolic health.

A Compendium on Hypertension: New Advances and Future Impact.

A Compendium on Hypertension: New Advances and Future Impact.

The Pivotal Role of Adipocyte-Na K peptide in Reversing Systemic Inflammation in Obesity and COVID-19 in the Development of Heart Failure.

This review summarizes data from several laboratories that have demonstrated a role of the Na/K-ATPase, specifically its α1 subunit, in the generation of reactive oxygen species (ROS) via the negative regulator of Src. Together with Src and other signaling proteins, the Na/K-ATPase forms an oxidant amplification loop (NKAL), amplifies ROS, and participates in cytokines storm in obesity. The development of a peptide fragment of the α1 subunit, NaKtide, has been shown to negatively regulate Src. Several groups showed that the systemic administration of the cell permeable modification of NaKtide (pNaKtide) or its selective delivery to fat tissue—adipocyte specific expression of NaKtide—ameliorate the systemic elevation of inflammatory cytokines seen in chronic obesity. Severe acute respiratory syndrome – coronavirus 2 (SARS-CoV-2), the RNA Coronavirus responsible for the COVID-19 global pandemic, invades cells via the angiotensin converting enzyme 2 (ACE-2) receptor (ACE2R) that is appended in inflamed fat tissue and exacerbates the formation of the cytokines storm. Both obesity and heart and renal failure are well known risks for adverse outcomes in patients infected with COVID-19. White adipocytes express ACE-2 receptors in high concentration, especially in obese patients. Once the virus invades the white adipocyte cell, it creates a COVID19–porphyrin complex which degrades and produces free porphyrin and iron and increases ROS. The increased formation of ROS and activation of the NKAL results in a further potentiated formation of ROS production, and ultimately, adipocyte generation of more inflammatory mediators, leading to systemic cytokines storm and heart failure. Moreover, chronic obesity also results in the reduction of antioxidant genes such as heme oxygenase-1 (HO-1), increasing adipocyte susceptibility to ROS and cytokines. It is the systemic inflammation and cytokine storm which is responsible for many of the adverse outcomes seen with COVID-19 infections in obese subjects, leading to heart failure and death. This review will also describe the potential antioxidant drugs and role of NaKtide and their demonstrated antioxidant effect used as a major strategy for improving obesity and epicardial fat mediated heart failure in the context of the COVID pandemic.

Вплив фізичних вправ на мікробіом кишечника та інсулінорезистентність у осіб з метаболічним синдромом

Metabolic syndrome is a cluster of cardiometabolic risk factors. They include obesity, dyslipidemia, hypertension, and insulin resistance. Central obesity and resistance to insulin, in particular, are recognized as causative factors, which form the development of metabolic syndrome. Metabolic syndrome is a progressive and genetically determined condition. The result of its progression is that carbohydrate, lipid and purine metabolism break down. The intestinal microbiome has a significant role in the pathogenesis of metabolic syndrome. One of the methods of influencing the micribiotic composition is the physical activity. The human intestinal microbiome is a complex ecosystem consisting not only of microorganisms, but also including bacteria, archaea, fungi and viruses. Biodiversity and the overall composition of the microbiota play a crucial role in maintaining normal homeostasis in the human body. With the recent advent of the possibility of studying the intestinal microbiome, the impact on its taxonomic composition and metabolism through exercise is the subject of scientific interest. Recent studies showed that the intestinal microbiota was directly involved in the formation of the metabolic syndrome. The function of the microbiome is just as important as the function of the "metabolic organs" that affect energy homeostasis and control body weight. In addition, changes in the intestinal microbiotic composition lead to increased intestinal permeability, endotoxemia, which plays a role in the development of chronic inflammation in the host, contributing to the development of metabolic syndrome and related chronic metabolic diseases. Intestinal microbiota in its own right is injected into the development of systemic inflammation in obesity, such a rank, inappropriate insertions in development or regression of insulin resistance, and hyperglycemia in metabolic syndrome. Physical activity can affect not only the composition of the microbial composition, but also the metabolic activity of the intestinal microbiome. The health-improving effect of physical exercises is connected with their ability to change the composition of an intestinal microbiota. Studies involving professional athletes and a specially selected control group indicated that athletes had a lower pro-inflammatory status and a high degree of bacterial diversity. Due to this, there is a positive dynamics of improving carbohydrate metabolism and the impact on the course of pathological processes associated with the metabolic syndrome, through the introduction of regular physical activity. Conclusion. The literature review presents data on the metabolic syndrome, its pathogenesis and components of the spectrum of development of metabolic disorders. We also analyzed material on influence of gut microbiota on development of metabolic disturbances and inreraction of structure of a microbiotic composition with physical exercises

Two Pandemics Coalition: COVID-19 and Obesity

Abstract COVID-19 epidemic caused by an influenza-like virus strain (SARS-CoV-2) invaded the world. The World Health Organization (WHO) announced this infection outbreak as a global pandemic on 11 March 2020. From one day to another the number of new cases is growing and also the number of deaths. This infection emerged earlier in Wuhan City and rapidly spread throughout China and around the world since December 2019. Another silent pandemic disease spreading mainly in industrialized countries is obesity. The best example is US were about 34% of the Americans are obese. In actual context, it can be said there is a coalition of 2 pandemics. In Romania, obesity and overweight prevalence assessed by Predatorr study is at a high level: 34,7% overweight and 31,9% obesity. Systemic inflammation in obesity is the central mechanism leading to lung function decline. There are two main questions a) is obese more sensible to viral infection or b) potentially more contagious? The answer is positive to both. Recent WOF official position stated that obesity is a risk factor for developing severe forms of COVID-19. Donna Ryan’s message, as president of World Obesity Federation WOF,US emphasized at the beginning of April the risk for severe complications for persons with obesity who contracted the infection with SARS-CoV-2. Nutritional support in COVID-19 should prefer oral feeding, whenever is possible. A special attention should be dedicated to a healthy microbiome and intestinal immunity. Energy intake should be 25-30 kcal/body weight, with 1.2-2g/kg proteins. Enteral nutrition will be recommended in severe cases. Evidence is supporting the recommendation that for people at risk of developing COVID-19 to consider for few weeks a dosage of 10000UI/day of vitD3, than a maintainance dose of 5000 UI/day. The target must be to stabilize a level of 40-60 ng/ml for 25(OH) D concentration.Pulmonary rehabilitation, smoking cessation, included in a healthy lifestyle will be further steps after patients recovery from this infection. Facing this pandemic coalition, our messages should be stronger in stimulating prevention of obesity. Since more than a half of Romanian population is already overweight or obese, healthy lifestyle should become a daily prescription, not just a luxury recommendation. Daily, right messages from doctors acting like role models, in a partnership between general practitioner and other specialties like diabetologists, pneumologists, cardiologists, nutritionists will be efficient weapons against this cruel coalition: Obesity and COVID 19.

Two Pandemics Coalition: Covid-19 and Obesity

Abstract COVID-19 epidemic caused by an influenza-like virus strain (SARS-CoV-2) invaded the world. The World Health Organization (WHO) announced this infection outbreak as a global pandemic on 11 March 2020. From one day to another the number of new cases is growing and also the number of deaths. This infection emerged earlier in Wuhan City and rapidly spread throughout China and around the world since December 2019. Another silent pandemic disease spreading mainly in industrialized countries is obesity. The best example is US were about 34% of the Americans are obese. In actual context, it can be said there is a coalition of 2 pandemics. In Romania, obesity and overweight prevalence assessed by Predatorr study is at a high level: 34,7% overweight and 31,9% obesity. Systemic inflammation in obesity is the central mechanism leading to lung function decline. There are two main questions a) is obese more sensible to viral infection or b) potentially more contagious? The answer is positive to both. Recent WOF official position stated that obesity is a risk factor for developing severe forms of COVID-19. Donna Ryan’s message, as president of World Obesity Federation WOF, US emphasized at the beginning of April the risk for severe complications for persons with obesity who contracted the infection with SARS-CoV-2. Nutritional support in COVID-19 should prefer oral feeding, whenever is possible. A special attention should be dedicated to a healthy microbiome and intestinal immunity. Energy intake should be 25-30 kcal/body weight, with 1.2-2 g/kg proteins. Enteral nutrition will be recommended in severe cases. Evidence is supporting the recommendation that for people at risk of developing COVID-19 to consider for few weeks a dosage of 10000 UI/day of vitD3, than a maintainance dose of 5000 UI/day. The target must be to stabilize a level of 40-60 ng/ml for 25(OH) D concentration. Pulmonary rehabilitation, smoking cessation, included in a healthy lifestyle will be further steps after patients recovery from this infection. Facing this pandemic coalition, our messages should be stronger in stimulating prevention of obesity. Since more than a half of Romanian population is already overweight or obese, healthy lifestyle should become a daily prescription, not just a luxury recommendation. Daily, right messages from doctors acting like role models, in a partnership between general practitioner and other specialties like diabetologists, pneumologists, cardiologists, nutritionists will be efficient weapons against this cruel coalition: Obesity and COVID 19.

Leptin in the regulation of the immunometabolism of adipose tissue-macrophages.

Obesity is a pandemic disease affecting around 15% of the global population. Obesity is a major risk factor for other conditions, such as type 2 diabetes and cardiovascular diseases. The adipose tissue is the main secretor of leptin, an adipokine responsible for the regulation of food intake and energy expenditure. Obese individuals become hyperleptinemic due to increased adipogenesis. Leptin acts through the leptin receptor and induces several immunometabolic changes in different cell types, including adipocytes and Mϕs. Adipose tissue resident Mϕs (ATMs) are the largest leukocyte population in the adipose tissue and these ATMs are in constant contact with the excessive leptin levels secreted in obese conditions. Leptin activates both theJAK2-STAT3and thePI3K-AKT-mTORpathways. The activation of these pathways leads to intracellular metabolic changes, with increased glucose uptake, upregulation of glycolytic enzymes, and disruption of mitochondrial function, as well as immunologic alterations, such as increased phagocytic activity and proinflammatory cytokines secretion. Here, we discuss the immunometabolic effects of leptin in Mϕs and how hyperleptinemia can contribute to thelow-gradesystemic inflammation in obesity.

Metabolic aspects of the relationship of asthma and obesity

Asthma and obesity are serious medical and social world problems, and their combined course is characterized by a decrease in the quality of life, an increase in the frequency and duration of hospitalization. The present review summarizes the current views on the mechanisms of formation of asthma phenotype combined with obesity, role of leptin and adiponectin imbalance in the development of systemic inflammation in obesity in the pathophysiology of asthma, its interrelations with metabolic syndrome. We present data that shows that syndrome is closely related not only to the debut of asthma, but also to a decrease in its control. Along with obesity, the role of other components of metabolic syndrome, in particular insulin resistance, as a predictor of asthma development is considered. Insulin resistance may be the most likely factor in the relationship between asthma and obesity, independent of other components of the metabolic syndrome. Insulin resistance associated with obesity can lead to disruption of nitric oxide synthesis. We reveal common mechanism of metabolic disorders of nitric oxide and arginine in metabolic syndrome and asthma and show that insulin resistance treatment can be therapeutically useful in patients with asthma in combination with obesity.

Myricetin-induced brown adipose tissue activation prevents obesity and insulin resistance in db/db mice

Myricetin, a dietary flavonoid, is effective in the treatment of obesity and insulin resistance by increasing glucose transport and lipogenesis in adipocyte and diminishing systemic inflammation in obesity. However, it has not been revealed yet whether myricetin is associated with brown adipose tissue (BAT) activation that tightly mediates systemic energy metabolism. Therefore, this study assessed whether myricetin activated brown adipose tissue in db/db mouse. Myricetin (400mg/kg) in distilled water was fed daily by oral gavage to leptin receptor-deficient db/db male mice at 4 weeks of age for 14 weeks. Body weight change, glucose intolerance test, blood lipid profile and BAT activation using PET-CT were assessed. After myricetin treatment for 14 weeks, systemic insulin resistance and hepatic steatosis were significantly improved in db/db mice with body weight reduction and myricetin led to decreased adipocity, improved plasma lipid profiles and increased energy expenditure. Myricetin activated BAT by upregulating thermogenic protein expression and activating mitochondrial biogenesis, eventually increasing heat dissipation in skin after cold exposure. In iWAT, myricetin induced beige formation, increased thermogenic protein expression and activated mitochondrial biogenesis. Consistently, thermogenic gene expression was upregulated when myricetin was introduced in C3H10T1/2 cells during brown adipocytes differentiation. Moreover, the expression level of adiponectin was significantly increased in C3H10T1/2 cells, adipose tissues and plasma after myricetin treatment. These results highlight that myricetin prevents obesity and systemic insulin resistance by activating BAT and increasing adiponectin expression in BAT.