Obesity-related Inflammation Research Articles

Longitudinal Changes in MR Elastography–based Biomarkers in Obese Patients Treated with Bariatric Surgery

Obesity-related chronic inflammation contributes to nonalcoholic fatty liver disease (NAFLD) progression in obese patients (body mass index [BMI] >30 kg/m2).1 The early detection of inflammation with noninvasive imaging technology may help identify individuals with a high risk of developing NAFLD.

Chromatin accessibility analysis identifies the transcription factor ETV5 as a suppressor of adipose tissue macrophage activation in obesity

Activation of adipose tissue macrophages (ATMs) contributes to chronic inflammation and insulin resistance in obesity. However, the transcriptional regulatory machinery involved in ATM activation during the development of obesity is not fully understood. Here, we profiled the chromatin accessibility of blood monocytes and ATMs from obese and lean mice using assay for transposase-accessible chromatin sequencing (ATAC-seq). We found that monocytes and ATMs from obese and lean mice exhibited distinct chromatin accessibility status. There are distinct regulatory elements that are specifically associated with monocyte or ATM activation in obesity. We also discovered several transcription factors that may regulate monocyte and ATM activation in obese mice, specifically a predicted transcription factor named ETS translocation variant 5 (ETV5). The expression of ETV5 was significantly decreased in ATMs from obese mice and its downregulation was mediated by palmitate stimulation. The decrease in ETV5 expression resulted in macrophage activation. Our results also indicate that ETV5 suppresses endoplasmic reticulum (ER) stress and Il6 expression in macrophages. Our work delineates the changes in chromatin accessibility in monocytes and ATMs during obesity, and identifies ETV5 as a critical transcription factor suppressing ATM activation, suggesting its potential use as a therapeutic target in obesity-related chronic inflammation.

Pediatric Obesity-Related Asthma: The Role of Nutrition and Nutrients in Prevention and Treatment.

Childhood obesity rates have dramatically risen in numerous countries worldwide. Obesity is likely a factor in increased asthma risk, which is already one of the most widespread chronic respiratory pathologies. The pathogenic mechanism of asthma risk has still not yet been fully elucidated. Moreover, the role of obesity-related inflammation and pulmonary overreaction to environmental triggers, which ultimately result in asthma-like symptoms, and the importance of dietary characteristics is well recognized. Diet is an important adjustable element in the asthma development. Food-specific composition of the diet, in particular fat, sugar, and low-quality nutrients, is likely to promote the chronic inflammatory state seen in asthmatic patients with obesity. An unbalanced diet or supplementation as a way to control asthma more efficiently has been described. A personalized dietary intervention may improve respiratory symptoms and signs and therapeutic response. In this narrative review, we presented and discussed more recent literature on asthma associated with obesity among children, focusing on the risk of asthma among children with obesity, asthma as a result of obesity focusing on the role of adipose tissue as a mediator of systemic and local airway inflammation implicated in asthma regulation, and the impact of nutrition and nutrients in the development and treatment of asthma. Appropriate early nutritional intervention could possibly be critical in preventing and managing asthma associated with obesity among children.

Tim-1 Deficiency Aggravates High-Fat Diet-Induced Steatohepatitis in Mice.

Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is commonly associated with obesity and characterized by excessive lipid accumulation and liver inflammation. The T cell immunoglobulin and mucin domain 1 (Tim-1), also known as hepatitis A virus cellular receptor 1 (Havcr-1) and kidney injury molecule 1 (Kim-1), has been shown to affect innate immunity-driven proinflammatory cascade in liver ischemia-reperfusion injury. However, its contribution to obesity-related NAFLD/NASH remains unknown. Thus, this study was designed to evaluate the role of Tim-1 in obesity-related liver inflammation and injury in wild-type (WT) and Tim-1-deficient (Tim-1-/-) C57BL/6J mice fed a high-fat diet (HFD) for 5-6 months. HFD feeding induced steatosis and upregulated Tim-1 gene expression in the liver of WT mice. Surprisingly, Tim-1-/- mice on HFD diet exhibited an exacerbation of hepatic steatosis, accompanied with an elevation of protein levels of fatty acid translocase CD36 and sterol regulatory element binding protein 1 (SREBP1). Tim-1 deficiency also enhanced HFD-induced liver inflammation and injury, as evidenced by augmented increase in hepatic expression of pro-inflammatory factor lipocalin 2 and elevated serum alanine transaminase (ALT). In addition, gene expression of type I, III and IV collagens and liver fibrosis were greatly enhanced in HFD Tim-1-/- mice compared with HFD WT mice. HFD-induced hepatic expression of YM-1, a specific mouse M2 macrophage marker, was further upregulated by deletion of Tim-1. Together, these results show that Tim-1 deficiency aggravates the effects of HFD diet on lipid accumulation and liver fibrosis, most likely through enhanced infiltration and activation of inflammatory cells.

The Relationship between Serum Procalcitonin and Dialysis Adequacy in Hemodialysis Patients

Introduction:In hemodialysis (HD) patients procalcitonin (PCT) considered as an early predictor of acute infection. It represents a new and potential marker of inflammation and may correlate with dialysis adequacy. This makes procalcitonin a potential biomarker for obesity-related low-grade inflammation. Objective: The aim of the work was to assess procalcitonin level in obese prevalent hemodialysis patients and its relation to hemodialysis adequacy. Patients and Methods: A cross sectional study was conducted on 90 patients divided into 3 groups, 40 obese (BMI ≥ 30 Kg/m2) ESRD patients on regular hemodialysis (group A), 40 non obese (BMI < 25Kg/m2) ESRD patients on regular hemodialysis (group B) attending at Dialysis Unit, El-Sahel Teaching Hospital and 10 healthy individuals with BMI < 25Kg/m2 as a control group (group C). All patients were subjected to detailed history taking and general examination. All patients were laboratory investigated for CBC, serum urea, creatinine, CRP, urea reduction ratio (URR), equilibrated Kt/v. All controls were subjected to written informed consent, full history, examination and CRP level. Procalcitonin level was done by ELISA technique for all patients and controls. Results: In our study, we found that there was a higher level of procalcitonin (PCT) in obese hemodialysis patient than non-obese. We also found that there was no correlation between PCT and hemodialysis adequacy in our study population. Conclusion: It could be concluded that procalcitonin is a potential biomarker for obesity-related low-grade inflammation, but not related to hemodialysis adequacy.

Modulation of Inflammatory Pathways and Adipogenesis by the Action of Gentisic Acid in RAW 264.7 and 3T3-L1 Cell Lines.

Gentisic acid (GA), a benzoic acid derivative present in various food ingredients, has been shown to have diverse pharmaceutical activities such as anti-carcinogenic, antioxidant, and hepatoprotective effects. In this study, we used a co-culture system to investigate the mechanisms of the anti-inflammatory and anti-adipogenic effects of GA on macrophages and adipocytes, respectively, as well as its effect on obesity-related chronic inflammation. We found that GA effectively suppressed lipopolysaccharide-stimulated inflammatory responses by controlling the production of nitric oxide and pro-inflammatory cytokines and modulating inflammation-related protein pathways. GA treatment also inhibited lipid accumulation in adipocytes by modulating the expression of major adipogenic transcription factors and their upstream protein pathways. Furthermore, in the macrophage-adipocyte co-culture system, GA decreased the production of obesity-related cytokines. These results indicate that GA possesses effective anti-inflammatory and anti-adipogenic activities and may be used in developing treatments for the management of obesity-related chronic inflammatory diseases.

Estrogen Receptor Beta (ERβ) Maintains Mitochondrial Network Regulating Invasiveness in an Obesity-Related Inflammation Condition in Breast Cancer.

Obesity, a physiological situation where different proinflammatory cytokines and hormones are secreted, is a major risk factor for breast cancer. Mitochondrial functionality exhibits a relevant role in the tumorigenic potential of a cancer cell. In the present study, it has been examined the influence of an obesity-related inflammation ELIT treatment (17β-estradiol, leptin, IL-6, and TNFα), which aims to stimulate the hormonal conditions of a postmenopausal obese woman on the mitochondrial functionality and invasiveness of MCF7 and T47D breast cancer cell lines, which display a different ratio of both estrogen receptor isoforms, ERα and ERβ. The results showed a decrease in mitochondrial functionality, with an increase in oxidative stress and invasiveness and motility, in the MCF7 cell line (high ERα/ERβ ratio) compared to a maintained status in the T47D cell line (low ERα/ERβ ratio) after ELIT treatment. In addition, breast cancer biopsies were analyzed, showing that breast tumors of obese patients present a high positive correlation between IL-6 receptor and ERβ and have an increased expression of cytokines, antioxidant enzymes, and mitochondrial biogenesis and dynamics genes. Altogether, giving special importance to ERβ in the pathology of obese patients with breast cancer is necessary, approaching to personalized medicine.

Antioxidant and anti-inflammatory properties of gamma- oryzanol attenuates insulin resistance by increasing GLUT- 4 expression in skeletal muscle of obese animals

BackgroundSkeletal muscle is the most important organ for whole-body glucose homeostasis. However, it has been suggested that obesity-related inflammation could be involved in insulin resistance and diabetes mellitus type 2 (DM2) development due several mechanisms, among them, the reduced expression of the glucose transporter type 4 (GLUT-4). Gamma-oryzanol (γOz) is a compound present in the whole grain of rice that presents anti-inflammatory and antioxidant activities. The aim of this study was to verify if the effect antioxidant and anti-inflammatory of yOz attenuate insulin resistance in skeletal muscle of obese rats by increasing GLUT- 4 expression. MethodsMale Wistar rats (±187 g) were initially randomly distributed into 2 experimental groups (control, n = 6, and high sugar-fat diet (HSF), n = 12) for 20 weeks. At week 20th of this study, once obesity and insulin resistance were detected in the HSF group, animals were divided to begin the treatment with γOz or continue receiving HSF for 10 more weeks. At the end it was analyzed nutritional, metabolic, inflammatory and oxidative stress parameters and GLUT-4 protein expression. ResultsThe treatment improved insulin resistance, reduced inflammation, increased antioxidant response and GLUT-4 expression. ConclusionIt is possible to conclude that the antioxidant and anti-inflammatory activity of yOz attenuates insulin resistance by increasing GLUT-4 expression in skeletal muscle of obese animals.

Oleanolic Acid Improves Obesity-Related Inflammation and Insulin Resistance by Regulating Macrophages Activation.

The chronic low-grade inflammation of adipose tissues, primarily mediated by adipose tissue macrophages (ATMs), is the key pathogenic link between obesity and metabolic disorders. Oleanolic acid (OA) is a natural triterpenoid possessing anti-diabetic and anti-inflammation effects, but the machinery is poorly understood. This study investigated the detailed mechanisms of OA on adipose tissue inflammation in obese mice. C57BL/6J mice were fed with high-fat diet (HFD) for 12 weeks, then daily intragastric administrated with vehicle, 25 and 50 mg/kg OA for 4 weeks. Comparing with vehicle, OA administration in obese mice greatly improved insulin resistance, and reduced adipose tissue hypertrophy, ATM infiltration as well as the M1/M2 ratio. The pro-inflammatory markers were significantly down-regulated by OA in both adipose tissue of obese mice and RAW264.7 macrophages treated with interferon gamma/lipopolysaccharide (IFN-γ/LPS). Furthermore, it was found that OA suppressed activation of mitogen-activated protein kinase (MAPK) signaling and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome through decreasing voltage dependent anion channels (VDAC) expression and reactive oxygen species (ROS) production. This is the first report that oleanolic acid exerts its benefits by affecting mitochondrial function and macrophage activation.

1213-P: A Novel Relationship between Thromboxane A2 Receptor and Obesity-Related Inflammation

Animal models of obesity have shown that the expression of Thromboxane A2 Receptor (tbxa2r) and thromboxane synthase (Tbxas1) are increased in adipose tissue (AT) and are associated with insulin resistance and inflammation. Objective: To compare Tbxa2r gene expression in the AT of human subjects with different degrees of obesity and to determine the association between AT Tbxa2r with BMI and markers of AT inflammation. Methods: Subcutaneous AT samples were collected from lean (BMI 40) subjects. Gene expression of Tbxa2r was analyzed in AT and compared among different groups. Correlation analysis to determine the association between AT Tbxa2r and obesity and obesity-related inflammation. Results: The mRNA levels of Tbxa2r were significantly higher in obese compared to normal subjects (P Conclusion: Signaling of TxA2 is higher in AT in obesity and is associated with BMI as well as inflammatory genes. Tbxa2r may be a potential therapeutic target for obesity-linked diseases including type 2 DM and CV disease. Disclosure D. Alcaraz alvarez: None. S. Viswanathan: None. T. Gopal: None. N. Kumar: None. K. Kelley: None. C. Desouza: Advisory Panel; Self; Bayer AG, Novo Nordisk, Consultant; Self; AstraZeneca.

Dark Sweet Cherry (DSC) Juice Consumption for Obesity-Related Inflammation and Cognitive Function in Obese Adults: A Human Clinical Pilot Trial

ObjectivesTo assess the effects of DSC juice on biomarkers of obesity-related metabolic disorders, inflammation, and cognitive performance. MethodsEligible participants (>18, body-mass index (BMI) = 30–40 kg/m2, no history of chronic disease and/or medication/antibiotics), were assigned to cherry or placebo groups following a single-blind randomized design after a 2-week run-in period. Participants were asked to drink 200 mL cherry juice supplemented with 3 g DSC powder (n = 11) or placebo drink (n = 10) twice a day for 30 days. Wellness check, anthropometric measurements, cognitive function/psychological assessments, and fasting blood samples were collected at study days 1 and 30. ResultsBaseline data showed no differences in anthropometric measurements between experimental groups. Results from blood markers of liver and metabolic disorders showed no difference between end point and baseline values for both cherry and placebo groups. However, median (25%, 75% interquartile) values for erythrocyte sedimentation rate (ESR) and reactive oxygen species (ROS) at day 30 (ESR = 6 (4, 13), ROS = 29 (13, 53) showed improvement compared to day 1 (ESR = 7 (2, 16), ROS = 33 (21, 65)) in cherry group, while in placebo group values showed less or no improvement (ESR = 12 (8, 24), ROS = 30 (20, 72) at day 30), vs (ESR = 10 (7, 18), ROS = 37 (29, 75) at day 1). These results suggest an anti-inflammatory cherry juice action and may be correlated with a trend for improvement in all of the cognitive tasks and physiological assessments in cherry group. The trail making tests (A and B), which assess executive functioning, improved (P = 0.0273 and P = 0.0342, respectively) as well as the Digit Span Forward task (DSF) (P = 0.0137), which examines short-term memory storage and executive control processes. The Digit Symbol Substitution test (DSST) used to assess processing speed, sustained attention and working memory showed improvement for cherry group, although non-significant (P = 0.0527). ConclusionsThese preliminary findings suggest that consumption of DSC juice rich in anthocyanins and other phytochemicals over 4 weeks may improve cognitive function in obese participants with possible link to lowered inflammation. Funding SourcesThis work was supported by the Northwest Cherry Growers.

Inflammation-related plasma protein levels and association with adiposity measurements in young adults

Obesity-related inflammation is associated with cardiovascular, metabolic, and pulmonary diseases. The aim of this study was to demonstrate associations between adiposity measurements and levels of inflammation-related plasma proteins in a population of young adults. Subjects from a population-based birth cohort with a mean age of 22.5 years were included in the study population (n = 2074). Protein levels were analyzed using the Olink Proseek Multiplex Inflammation panel. Percentage body fat (%BF) and visceral fat rating (VFR) measurements were collected using Tanita MC 780 body composition monitor. Linear regression of standardized values was used to investigate associations. Potential effect modifications by sex and BMI category were assessed. Of 71 investigated proteins, 54 were significantly associated with all adiposity measurements [%BF, body mass index (BMI), VFR and waist circumference]. Among proteins associated with %BF, seven showed a larger or unique association in overweight/obese subjects and three showed a significant effect modification by sex. Fourteen proteins more strongly associated with VFR in females compared to males. Adipose-associated systemic inflammation was observed in this young adult population. Sex and adiposity localization influenced some of the associations. Our results highlight specific proteins as suitable biomarkers related to adiposity.

Obesity-Related Inflammation and Endothelial Dysfunction in COVID-19: Impact on Disease Severity.

The coronavirus disease 2019 (COVID-19) pandemic has put into evidence another pandemic – obesity. Currently, several studies have documented the association between obesity and COVID-19 severity. The mechanisms underlying the increased risk of complications and mortality in obese patients with COVID-19 are of diverse nature. Inflammation plays a central role in obesity. Metabolic alterations seen in obese patients are related to an inflammatory response, and several studies report elevated levels of circulating inflammatory cytokines in obese patients. Also, deregulated expression of adipokines, such as leptin and resistin, increase the expression of vascular adhesion molecule 1 and intercellular adhesion molecule 1 that contribute to increased vascular leukocyte adhesiveness and additional oxidative stress. Additionally, it is now recognized that the chronic impairment of systemic vascular endothelial function in patients with cardiovascular and metabolic disorders, including obesity, when intensified by the detrimental effects of SARS-CoV-2 over the endothelium, may explain their worse outcomes in COVID-19. In fact, vascular endothelial dysfunction may contribute to a unfavorable response of the endothelium to the infection by SARS-CoV-2, whereas alterations in cardiac structure and function and the prothrombotic environment in obesity may also provide a link to the increased cardiovascular events in these patients.

Microbiome Dysbiosis in Obese Adolescents: A Potential Contributor to Inflammation

Introduction Adolescent obesity remains a public health concern, as the CDC estimates that 1 in 5 adolescents is obese. The development of obesity during childhood not only increases the chance of obesity-related death, but also increases the risk of obesity-related chronic diseases such as type 2 diabetes mellitus, hypertension, and dyslipidemia. Increased inflammation is associated with adipose tissue in obesity and is a main contributor to the development of obesity-related disease. Dysbiosis of the gut microbiome may also contribute to obesity-related systemic inflammation. In this study, patients were educated on dietary habits and exercise in an effort to understand the effect of lifestyle changes on inflammatory markers in the urine. Furthermore, we investigated the gut microbiome profiles of obese adolescents to determine if differences existed from that of healthy adolescents. Methods The study was performed at the Department of Pediatrics at TTUHSC, Amarillo. IRB approval was obtained, and informed consent/assent were signed by the parents and adolescents. Twenty-two obese adolescents ages 8-18 (BMI >25) and 16 healthy adolescents (BMI <25) were recruited into the study. At the start of the study, patients were educated on dietary changes and exercise. Urine samples were collected at enrollment, and at 3- and 6-months post-enrollment visits. Urine samples were analyzed for the presence of pro-inflammatory cytokines TNF-a and IL-6, as well as the marker for endothelial dysfunction, ET-1. Stool samples were procured at the time of enrollment and 16s metagenome sequencing was performed to determine microbiome composition. Results Adolescents with obesity exhibited higher levels of pro-inflammatory TNF-α and IL-6 (3.4 and 1.6-fold increase, respectively) in urine compared to healthy controls. Furthermore, we noted a 1.4-fold increase in urinary ET-1 of obese adolescents. Interestingly, TNF-a, IL-6, and ET-1 levels in the urine decreased in obese adolescents over a period of 6 months, suggesting that changes in diet and exercise may have contributed to these changes. Analysis of the 16s metagenome indicated a difference in the presence of 80 bacterial species between the gut microbiomes of healthy and obese adolescents, as healthy adolescents had 63 bacterial species that exhibited at least a 2-fold higher amount than obese adolescents. Conclusions Obesity is a preventable condition that can result in systemic inflammation and chronic disease. In this study, we found that obese adolescents exhibited higher levels of urinary inflammatory cytokines and altered gut microbiome composition compared to healthy controls. Furthermore, we noted that lifestyle changes over 6 months resulted in decreased urinary inflammatory markers in obese adolescents. The results of this study suggest that the altered gut microbiomes of obese adolescents may be responsible for increased urinary inflammatory cytokine levels and that lifestyle changes may attenuate urinary inflammatory cytokines.

Impact of Obesity-Induced Inflammation on Cardiovascular Diseases (CVD).

Overweight and obesity are key risk factors of cardiovascular disease (CVD). Obesity is currently presented as a pro-inflammatory state with an expansion in the outflow of inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), alongside the expanded emission of leptin. The present review aimed to evaluate the relationship between obesity and inflammation and their impacts on the development of cardiovascular disease. A literature search was conducted by employing three academic databases, namely PubMed (Medline), Scopus (EMBASE), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). The search presented 786 items, and by inclusion and exclusion filterers, 59 works were considered for final review. The Newcastle–Ottawa Scale (NOS) method was adopted to conduct quality assessment; 19 papers were further selected based on the quality score. Obesity-related inflammation leads to a low-grade inflammatory state in organisms by upregulating pro-inflammatory markers and downregulating anti-inflammatory cytokines, thereby contributing to cardiovascular disease pathogenesis. Because of inflammatory and infectious symptoms, adipocytes appear to instigate articulation and discharge a few intense stage reactants and carriers of inflammation. Obesity and inflammatory markers are strongly associated, and are important factors in the development of CVD. Hence, weight management can help prevent cardiovascular risks and poor outcomes by inhibiting inflammatory mechanisms.

CC chemokine ligand 2 (CCL2) stimulates aromatase gene expression in mammary adipose tissue.

Obesity is a risk factor for postmenopausal breast cancer. Obesity-related inflammation upregulates aromatase expression, the rate-limiting enzyme for estrogen synthesis, in breast adipose tissue (BAT), increasing estrogen production and cancer risk. The regulation of aromatase gene (CYP19A1) in BAT is complex, and the mechanisms linking obesity and aromatase dysregulation are not fully understood. An obesity-associated factor that could regulate aromatase is the CC chemokine ligand (CCL) 2, a pro-inflammatory factor that also activates signaling pathways implicated in CYP19A1 transcription. By using human primary breast adipose stromal cells (ASCs) and aromatase reporter (hARO-Luc) mouse mammary adipose explants, we demonstrated that CCL2 enhances the glucocorticoid-mediated CYP19A1 transcription. The potential mechanism involves the activation of PI.4 via ERK1/2 pathway. We also showed that CCL2 contributes to the pro-inflammatory milieu and aromatase expression in obesity, evidenced by increased expression of CCL2 and CYP19A1 in mammary tissues from obese hARO-Luc mice, and subcutaneous adipose tissue from obese women. In summary, our results indicate that postmenopausal obesity may promote CCL2 production in BAT, leading to exacerbation of the menopause-related inflammatory state and further stimulation of local aromatase and estrogens. These results provide new insights into the regulation of aromatase and may aid in finding approaches to prevent breast cancer.

Small Airway Dysfunction Links Asthma Severity with Physical Activity and Symptom Control

Little is known about the role of small airway dysfunction (SAD) and its complex relation with asthma control and physical activity (PA). To investigate the interrelations among SAD, risk factors for asthma severity, symptom control, and PA. We assessed SAD by impulse oscillometry and other sophisticated lung function measures including inert gas washout in adults with asthma (mild to moderate, n= 140; severe, n= 128) and 69 healthy controls from the All Age Asthma Cohort. We evaluated SAD prevalence and its interrelation with risk factors for asthma severity (older age, obesity, and smoking), type 2 inflammation (sputum and blood eosinophils, fractional exhaled nitric oxide), systemic inflammation (high-sensitivity C-reactive protein), asthma control (AC), and PA (accelerometer for 1 week). We applied a clinical model based on structural equation modeling that integrated causal pathways among these clinical variables. The prevalence of SAD ranged from 75% to 90% in patients with severe asthma and from 53% to 64% in mild to moderate asthma. Severe SAD was associated with poor AC and low PA. Structural equation modeling indicated that age, obesity, obesity-related systemic inflammation, T2 inflammation, and smoking are independent predictors of SAD. Small airway dysfunction was the main determinant factor of AC, which in turn affected PA. Obesity affected AC directly and through its contribution to SAD and low PA. In addition, PA had bidirectional associations with obesity, SAD, and AC. Structural equation modeling also indicated interrelations among distal airflow limitation, air trapping, and ventilation heterogeneity. Small airway dysfunction is a highly prevalent key feature of asthma that interrelates a spectrum of distal lung function abnormalities with risk factors for asthma severity, asthma control, and physical activity.

Long-Term Improvement of Chronic Low-Grade Inflammation After Bariatric Surgery

PurposeBariatric surgery (BS) was shown to improve inflammatory markers in previous short-term follow-up studies. The aim of the present study was to assess the long-term effects of BS on chronic low-grade inflammation markers related to severe obesity. Moreover, the meaning of the type of BS procedure as well as the remission of type 2 diabetes (T2D) for inflammatory status up to 4 years after BS was analyzed.Materials and MethodsIn a retrospective cohort study including 163 patients at baseline, inflammatory and metabolic parameters were assessed at 4 time points: before surgery (baseline), 6 months after surgery (visit 1), 2 years after surgery (visit 2), and 4 years after surgery (visit 3). Univariate regression analysis was used to identify variables that were thought to determine change in inflammatory parameters.ResultsCRP, hs-CRP, leucocytes, and ferritin significantly declined in the mid- and long-term according to the U-shaped curve of weight loss (p<0.001). Change in body mass index (BMI) at long-time follow-up showed a significant linear effect on change in leucocytes (B=0.082; p<0.001) and change in hs-CRP (B=0.03; p<0.05). There was a strong, positive correlation between T2D and hs-CRP at visit 2 (rs=0.195; p<0.05) and visit 3 (rs=0.36; p=0.001). With regard to type of surgery and gender, there were no significant differences in inflammatory parameters.ConclusionBS is able to reduce obesity-related chronic low-grade inflammation up to 4 years after surgical intervention. The improvement in metaflammation is related to the change in BMI and remission of T2D in the long-term.Graphical abstract

Targeted peripheral focused ultrasound stimulation attenuates obesity-induced metabolic and inflammatory dysfunctions

Obesity, a growing health concern, is associated with an increased risk of morbidity and mortality. Chronic low-grade inflammation is implicated in obesity-driven metabolic complications. Peripheral focused ultrasound stimulation (pFUS) is an emerging non-invasive technology that modulates inflammation. Here, we reasoned that focused ultrasound stimulation of the liver may alleviate obesity-related inflammation and other comorbidities. After 8 weeks on a high-fat high-carbohydrate “Western” diet, C57BL/6J mice were subjected to either sham stimulation or focused ultrasound stimulation at the porta hepatis. Daily liver-focused ultrasound stimulation for 8 weeks significantly decreased body weight, circulating lipids and mitigated dysregulation of adipokines. In addition, liver-focused ultrasound stimulation significantly reduced hepatic cytokine levels and leukocyte infiltration. Our findings demonstrate the efficacy of hepatic focused ultrasound for alleviating obesity and obesity-associated complications in mice. These findings suggest a previously unrecognized potential of hepatic focused ultrasound as a possible novel noninvasive approach in the context of obesity.

Adipose Extracellular Vesicles in Intercellular and Inter-Organ Crosstalk in Metabolic Health and Diseases.

Adipose tissue (AT) is a highly heterogeneous and dynamic organ that plays important roles in regulating energy metabolism and insulin sensitivity. In addition to its classical roles in nutrient sensing and energy storage/dissipation, AT secretes a large number of bioactive molecules (termed adipokines) participating in immune responses and metabolic regulation through their paracrine and/or endocrine actions. Adipose-derived extracellular vesicles (ADEVs), including exosomes, microvesicles (MVs), and apoptotic bodies, have recently emerged as a novel class of signal messengers, mediating intercellular communications and inter-organ crosstalk. In AT, ADEVs derived from adipocytes, immune cells, mesenchymal stem cells, endothelial cells are actively involved in modulation of immune microenvironment, adipogenesis, browing of white adipose tissue, adipokine release and tissue remodeling. Furthermore, ADEVs exert their metabolic actions in distal organs (such as liver, skeletal muscle, pancreas and brain) by sending genetic information (mainly in the form of microRNAs) to their target cells for regulation of gene expression. Here, we provide an updated summary on the nature and composition of ADEVs, and their pathophysiological functions in regulating immune responses, whole-body insulin sensitivity and metabolism. Furthermore, we highlight the latest clinical evidence supporting aberrant production and/or function of ADEVs as a contributor to obesity-related chronic inflammation and metabolic complications and discuss the opportunities and challenges in developing novel therapies by targeting ADEVs.