Deep immune cell phenotyping and induced immune cell responses at admission stratified by BMI in patients hospitalized with COVID-19: An observational multicenter cohort pilot study.

INTRODUCTION: Overweight and obesity are linked to increased hospitalization and mortality in COVID-19 patients. This study aimed to characterize induced immune responses and deep immune cell profiles stratified by BMI in hospitalized COVID-19 patients. METHODS AND RESULTS: This observational multicenter cohort pilot study included 122 adult patients with PCR-confirmed COVID-19 in Denmark, stratified by BMI (normal weight, overweight, obese). Inflammation was assessed using TruCulture® and immune cell profiles by flow cytometry with a customized antibody panel (DuraClone®). Patients with obesity had a more pro-inflammatory phenotype with increased TNF-α, IL-8, IL-17, and IL-10 levels post-T cell stimulation, and altered B cell profiles. Patients with obesity showed higher concentrations of naïve, transitional, and non-isotype switched memory B cells, and plasmablasts compared to normal weight patients and healthy controls. CONCLUSIONS: Obesity in hospitalized COVID-19 patients may correlate with elevated pro-inflammatory cytokines, anti-inflammatory IL-10, and increased B cell subset activation, highlighting the need for further studies.

Calorie restriction-induced leptin reduction and T-lymphocyte activation in blood and adipose tissue in men with overweight and obesity.

BACKGROUND: T-Lymphocyte activation is modulated by the adipokine leptin and serum concentrations of this hormone can be reduced with short-term calorie restriction. The aim of this study was to understand whether leptin per se is important in determining levels of T-lymphocyte activation in humans, by investigating whether the reduction in leptin concentration following calorie restriction is associated with a decrease in T-Lymphocyte activation in blood and adipose tissue. METHODS: Twelve men with overweight and obesity (age 35-55 years, waist circumference 95-115 cm) reduced their calorie intake by 50% for 3 consecutive days. Blood and subcutaneous adipose tissue were obtained for isolation of immune cells and cytokine analysis. CD4+ and CD8 + T-Lymphocytes were identified and characterised according to their expression of activation markers CD25 and CD69 by flow cytometry. RESULTS: Serum leptin was reduced by (mean ± SEM) 31 ± 16% (p < 0.001) following calorie restriction. The percentage of blood CD4 + CD25 + T-lymphocytes and level of CD25 expression on these lymphocytes were significantly reduced by 8 ± 10% (p = 0.016) and 8 ± 4% (p = 0.058), respectively. After calorie restriction, ex vivo leptin secretion from abdominal subcutaneous adipose tissue explants was not changed, and this corresponded with a lack of change in adipose tissue resident T-Lymphocyte activation. CONCLUSIONS: Serum leptin was reduced after calorie restriction and this was temporally associated with a reduction in activation of blood CD4 + CD25 + T-Lymphocytes. In abdominal subcutaneous adipose tissue, however, leptin secretion was unaltered, and there were no observed changes in adipose resident T-Lymphocyte activation.

Characterizing Human Peripheral Blood Lymphocyte Phenotypes and Their Correlations with Body Composition in Normal-Weight, Overweight, and Obese Healthy Young Adults.

Background and Objectives: Obesity-associated chronic low-grade inflammation supports various systemic alterations. In this descriptive study, 122 apparently healthy adults aged 20 to 35 years were voluntarily included and classified based on body mass index (BMI) as normal-weight (NW), overweight (OW), and obese (OB). This study aims to characterize peripheral blood (PB) lymphocyte (Ly) phenotypes and investigate their correlations with body composition indices (BCIs) in healthy young adults. Materials and Methods: The following BCIs were measured: waist circumference, hip circumference, height, waist-to-hip ratio, waist-to-height ratio, total body fat mass, visceral fat level, weight, and BMI. White blood cell count (WBC), Ly absolute count, serum TNF-α, and IFN-γ were quantified. Ly subpopulations were analyzed as follows: total TLy (TTLy-CD45+CD3+), early activated TLy (EATLy-CD45+3+69+), total NKLy (TNKLy-CD45+CD3-CD56+CD16+), NKdim (low expression of CD56+), NKbright (high expression of CD56+), BLy (CD45+CD3-CD19+), T helper Ly (ThLy-CD45+CD3+CD4+), and T cytotoxic Ly (TcLy-CD45+CD3+CD8+). Results: Higher BMI has significantly higher WBC and BLy (p < 0.0001; p = 0.0085). EATLy significantly decreased from NW to OB (3.10-NW, 1.10-OW, 0.85-OB, p < 0.0001). Only EATLy exhibited significant negative correlations with all the BCIs. A significantly higher TNF-α was observed in the OW and OB groups compared to the NW group. IFN-γ increased linearly but nonsignificantly with BMI. TTLy showed a nonsignificant positive correlation with both IFN-γ and TNF-α, while EATLy showed a negative correlation, significant only for IFN-γ. NKLy subpopulations exhibited a consistent negative correlation with TNF-α, significant only for NKdim (p = 0.0423), and a nonsignificant consistent positive correlation with IFN-γ. A nonsignificant negative correlation between age and both TNKLy (r = -0.0927) and NKdim (r = -0.0893) cells was found, while a positive correlation was found with NKbright (r = 0.0583). Conclusions: In conclusion, the baseline immunological profile of PB is influenced by excessive adipose tissue in healthy young adults.

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects.

The IL-1 family member IL-38 (IL1F10) suppresses inflammatory and autoimmune conditions. Here, we report that plasma concentrations of IL-38 in 288 healthy Europeans correlate positively with circulating memory B cells and plasmablasts. IL-38 correlated negatively with age (p = 0.02) and was stable in 48 subjects for 1 year. In comparison with primary keratinocytes, IL1F10 expression in CD19+ B cells from PBMC was lower, whereas cell-associated IL-38 expression was comparable. In vitro, IL-38 is released from CD19+ B cells after stimulation with rituximab. Intravenous LPS in humans failed to induce circulating IL-38, compared to 100-fold induction of IL-6 and IL-1 receptor antagonist. In a cohort of 296 subjects with body mass index > 27 at high risk for cardiovascular disease, IL-38 plasma concentrations were significantly lower than in healthy subjects (p < 0.0001), and lowest in those with metabolic syndrome (p < 0.05). IL-38 also correlated inversely with high sensitivity C-reactive protein (p < 0.01), IL-6, IL-1Ra, and leptin (p < 0.05). We conclude that a relative deficiency of the B cell product IL-38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent with IL-38 as an anti-inflammatory cytokine.

Serum IL-35 is decreased in overweight patients with rheumatoid arthritis: its correlation with Th1/Th2/Th17-related cytokines.

BACKGROUND: Obesity is correlated with worse drug responses and high disease activity in patients with rheumatoid arthritis (RA). Interleukin (IL)-35 is a novel anti-inflammatory cytokine that mainly produced by regulatory T (Treg). This study was performed to analyze whether IL-35 was correlated with obesity in RA and investigate the correlation between other Th1/Th2/Th17-related cytokines and obesity in RA. RESULTS: The serum IL-35 level was analyzed in RA (n = 81) and healthy donors (n = 53) by ELISA assay, and was compared between three groups (body mass index (BMI) < 18.5,≥18.5 to 25, > 25). Serum cytokines including IL-2, IL-4, IL-10, IL-17, INF-γ, TNF-α levels were measured using Flowcytometry assay. Clinical information was extracted from medical records. Serum IL-35 level in overweight patients were significantly decreased than those in lean patients. Furthermore, Th1/Th2/Th17-related cytokines from overweight patients with RA showed the characteristic immunological features. Serum IL-6, IL-17 and TNF-α levels were positively correlated with BMI. However, serum IL-2, IL-4, IL-10 and IFN-γ concentrations were not correlated with BMI. CONCLUSIONS: Quantitative changes in serum IL-35 level were characteristic in overweight patients with RA. These findings indicate that IL-35 plays an important role in the development of RA and may prove to be a potential biomarker of active RA.

Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy.

PURPOSE: The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors' immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses. METHODS: The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient's height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and > 25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and < 30 kg/m2 were overweight (OW), and those ≥30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014. RESULTS: The median BMI was 21.9 kg/m2 (range, 14.3-38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p = 0.001; vs. OW: p = 0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p = 0.031). CONCLUSIONS: Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.

An Oily Fish Diet Improves Subclinical Inflammation in People at High Cardiovascular Risk: A Randomized Controlled Study.

Interest has arisen on the anti-inflammatory action of dietary components, including long-chain n-3 fatty acids (LCn3) and polyphenols (PP). The aim of this study was to evaluate the effects of diets rich in PP and oily fish (high-LCn3 diets) on markers of subclinical inflammation and growth factors in people at high cardiometabolic risk. Individuals with high waist circumference and one more component of metabolic syndrome were randomized to one of the following isoenergetic diets: low LCn3&PP, high LCn3, high PP, high LCn3&PP. Before and after 8 weeks, fasting and postprandial plasma concentrations of hs-CRP and fasting serum concentrations of IL-1, IL-4, IL-6, IL-10, IL-17, INF-, TNF-, FGF, VEGF, PDGF-, G-CSF, and GM-CSF were determined. An oily fish diet reduced fasting plasma hs-CRP (1.28 ± 12.0, -12.5 ± 6.9, 22.5 ± 33.6, -12.2 ± 11.9; 8-week percent change, Mean ± SEM; low LCn3&PP, high LCn3, high PP, high LCn3&PP group, respectively), postprandial 6h-AUC hs-CRP (4.6 ± 16.3, -18.2 ± 7.2, 26.9 ± 35.1, -11.5 ± 11.8, 8-week percent change) and fasting IL-6 (20.8 ± 18.7, -2.44 ± 12.4, 28.1 ± 17.4, -9.6 ± 10.2), IL-17 (2.40 ± 4.9, -13.3 ± 4.9, 3.8 ± 4.43, -11.5 ± 4.7), and VEGF (-5.7 ± 5.8, -5.6 ± 7.5, 3.5 ± 5.8, -11.1 ± 5.5) (8-week percent change; p < 0.05 for LCn3 effect for all; no significant effect for PP; 2-factor ANOVA). An oily fish diet improved subclinical inflammation, while no significant effect was observed for dietary polyphenols.

A Carbohydrate Beverage Reduces Monocytes Expressing TLR4 in Children with Overweight or Obesity.

BACKGROUND: Childhood obesity is increasing, with about one-third of children overweight or obese. Obesity is characterized by a state of chronic low-grade inflammation that is related to cardiometabolic comorbidities. Inflammatory monocytes, which are classified into 3 different groups-classical, intermediate, and nonclassical monocytes, with Toll-like receptor 4 (TLR4+) expression indicating a proinflammatory state-underlie several obesity-associated morbidities. OBJECTIVES: This study aimed to assess the responses of monocyte populations to beverages of differing macronutrient composition in children with healthy weight (HW) or overweight/obesity (OW/OB). METHODS: Ten HW children (5th to 84.9th percentile; mean age 12.29 ± 2.5 y) and 7 children with OW/OB (85th to 99.99th percentile; mean age 11.96 ± 3.8 y) completed the study. Adiposity was determined via DXA. Using a double-blinded, randomized, crossover design, participants consumed either a high-carbohydrate (CHO; 210 kcal; 0 g fat/56 g carbohydrates/0 g protein) or a whole-egg-based high-protein/fat (EGG; 210 kcal; 15 g fat/0 g carbohydrates/18 g protein) beverage. Venous blood was collected at baseline and 2 h postprandially for evaluation of metabolic and inflammatory responses. Repeated measures ANOVA and Pearson correlations were conducted. RESULTS: Consuming the CHO beverage significantly reduced the primary outcome: TLR4+ expression on classical monocytes in children with OW/OB only (25.60% decrease from baseline in OW/OB compared with 1.61% increase in HW). Children with OW/OB had significantly less percentages of TLR4+ nonclassical monocytes than HW (47.66% lower after CHO). Insulin and glucose (secondary outcomes), were significantly higher after the CHO condition compared with baseline (230.61% and 9.93% increase, respectively). Changes in glucose were significantly and negatively related to changes in monocyte populations in the CHO condition. CONCLUSIONS: These data suggest that high-carbohydrate beverages alter monocyte populations in the blood in children with OW/OB, which is related to glucose metabolism. These findings have implications for nutritional recommendations in children with overweight/obesity. National Clinical Trial registry trial number: NCT03597542.

Association between asthma, obesity, and health behaviors in African American youth.

Background: There is a clear relationship between obesity and asthma, with obesity recognized as a risk factor for asthma. There is mounting evidence, however, that asthma may predict obesity risk via behavioral pathways. Objectives: The purpose of this study was to assess the cross-sectional relationships between asthma, body mass index (BMI) percentile, and behavioral factors including caloric intake, dietary inflammatory index, moderate-vigorous physical activity (MVPA), and sedentary time (SED) among African American adolescents. Methods: A community-based sample of 195 African American youth (ages 11-18 years) were included in this analysis. Asthma status was based on self-report using the International Study of Asthma and Allergies in Children's Phase Three questionnaire. MVPA and SED were measured via accelerometry, and caloric intake and dietary inflammatory index were evaluated with the Food Frequency Questionnaire. Weight status was assessed via BMI percentile using measured weight, height, and CDC growth charts. Results: Adolescents with a history of asthma were significantly more overweight (62% vs. 43%, p = 0.04) and consumed a higher inflammatory diet (1.6 ± 0.3 vs. 1.0 ± 0.2, p = 0.02) than their peers who never had asthma. After adjusting for all covariates, activity and dietary variables, odds ratio analysis revealed adolescents who reported ever having asthma were 3.1 ± 1.5 times as likely to be overweight or obese than adolescents with no asthma history (p = 0.02). Conclusions: Presence of asthma history was associated with increased obesity risk in African American adolescents, independent of behavioral factors. Longitudinal studies are needed to better understand the relationship between asthma and obesity in African American adolescents.

Metabolic control of immune tolerance in health and autoimmunity.

The filed that links immunity and metabolism is rapidly expanding. The adipose tissue, by secreting a series of immune regulators called adipokines, represents the common mediator linking metabolic processes and immune system functions. The dysregulation of adipokine secretion, occurring in obese individuals or in conditions of malnutrition or dietary restriction, affects the activity of immune cells resulting in inflammatory autoimmune responses or increased susceptibility to infectious diseases. Alterations of cell metabolism that characterize several autoimmune diseases strongly support the idea that the immune tolerance is also regulated by metabolic pathways. The comprehension of the molecular mechanisms underlying these alterations may lead to the development of novel therapeutic strategies to control immune cell differentiation and function in conditions of autoimmunity.

Gut microbiota and overweight in 3-year old children.

BACKGROUND: The gut microbiota has been associated with overweight and obesity in adults, but the evidence in children is limited. Our aim was to study whether composition of the gut microbiota at the age of 3 years is associated with overweight/obesity in children cross-sectionally. METHODS: Children, who participated in a clinical trial of prenatal vitamin-D supplementation (VDAART), underwent standardized height and weight measurements, and collection of stool samples at 3 years of age. 16 S rRNA sequencing (V4 region) of the stool samples were performed with Illumina MiSeq. Associations between microbiota and overweight/obesity (body mass index z-scores >85th percentile) was analyzed using logistic regression. RESULTS: Out of 502 children, 146 (29%) were categorized as overweight/obese. Maternal pre-pregnancy BMI, birth weight and length, formula feeding during the first year, high frequency of fast food consumption, and time watching TV or computer screen at 3 years were the risk factors for overweight/obesity. Of the top 20 most abundant genera, high relative abundance of Parabacteroidetes (Bacteroidetes; Bacteroidales) (aOR(95% CI): 0.69 (0.53, 0.90, p = 0.007) per interquartile increase) and unassigned genus within Peptostreptococcae family were inversely associated with overweight/obesity, whereas high relative abundance of Dorea (Firmicutes;Clostridiales) (1.23 (1.05, 1.43, p = 0.009)) was positively associated. Associations were independent of each other. No associations were found between diversity indices and overweight/obesity. CONCLUSIONS: Our data suggest that some of the differences in gut composition of bacteria between obese and non-obese adults can already be observed in 3-year old children. Longitudinal studies will be needed to determine long-term effects.

Plasma endocannabinoid levels in lean, overweight, and obese humans: relationships to intestinal permeability markers, inflammation, and incretin secretion.

Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation; however, little is known of these effects in humans. This study aimed to 1) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl- sn-glycerol (2-AG), and OEA in humans; and 2) examine relationships to intestinal permeability, inflammation markers, and incretin hormone secretion. Twenty lean, 18 overweight, and 19 obese participants underwent intraduodenal Intralipid infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumor necrosis factor-α (TNFα), glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and Toll-like receptor 4 (TLR4) (by RT-PCR) were assessed. Fasting plasma AEA was increased in obese compared with lean and overweight patients ( P < 0.05), with no effect of BMI group or ID lipid infusion on plasma 2-AG or OEA. Duodenal expression of IAP and ZO-1 was reduced in obese compared with lean ( P < 0.05), and these levels related negatively to plasma AEA ( P < 0.05). The iAUC for AEA was positively related to iAUC GIP ( r = 0.384, P = 0.005). Obese individuals have increased plasma AEA and decreased duodenal expression of ZO-1 and IAP compared with lean and overweight subjects. The relationships between plasma AEA with duodenal ZO-1, IAP, and GIP suggest that altered endocannabinoid signaling may contribute to changes in intestinal permeability, inflammation, and incretin release in human obesity.

Oxidative balance score and serum γ-glutamyltransferase level among Korean adults: a nationwide population-based study.

PURPOSE: The oxidative balance score (OBS) comprises dietary and non-dietary lifestyle pro-oxidants and antioxidants. Elevated serum γ-glutamyltransferase (GGT) level has currently emerged as a biomarker of oxidative stress. In this study, we examined whether OBS was inversely associated with serum GGT level and whether OBS could be a useful marker to predict GGT among Korean adults. METHODS: This cross-sectional study was based on data obtained from the 2010 and 2011 Korea National Health and Nutrition Examination Survey. 2087 men and 2071 women were included in final analysis. The OBS was divided into five equal interval categories, and GGT was dichotomized into low and high using its sex-specific median value. Multiple logistic regression analysis was conducted to assess the association between OBS categories and high GGT. RESULTS: Compared with the lowest OBS category as reference, the multivariable adjusted ORs (95% CIs) for the highest OBS category of men and women were 0.05 (0.01-0.19) and 0.27 (0.09-0.78), respectively (p for trend <0.01). CONCLUSION: A higher OBS that indicates a predominance of antioxidant over pro-oxidant exposure was strongly inversely associated with GGT level among Korean adults.

Effects of supplementation with rice husk powder and rice bran on inflammatory factors in overweight and obese adults following an energy-restricted diet: a randomized controlled trial.

PURPOSE: Overweight and obesity are major public health concerns worldwide which are associated with a low-grade chronic inflammation. Dietary fiber as an important component of diet could be effective in controlling weight and inflammatory factors. The present study aimed to compare the effects of rice husk powder and rice bran on inflammatory factors along with an energy-restricted diet in overweight and obese adults. METHODS: In this randomized trial, 105 eligible individuals were assigned to one of the three energy-restricted diet groups receiving; rice bran (n = 35), rice husk powder (n = 35), and control group (n = 35) for 12 weeks. Demographic data, dietary intake, anthropometric indices and inflammatory factors (serum levels of IL-6 and hs-CRP) were measured at baseline and at the end of the study. RESULTS: Weight, BMI and waist circumference reduced significantly in all groups after 12 weeks of study (P < 0.01 for all). However, pre- and post-measure differences between groups were not significant. Moreover, serum levels of hs-CRP and IL-6 were not significantly different between participants in the rice bran or rice husk groups. However, the reduction in serum levels of hs-CRP in rice husk (mean change = - 0.14 ± 0.05 µg/ml) and rice bran (mean change = - 0.13 ± 0.03 µg/ml) was significantly higher when compared to the control group (mean change = - 0.03 ± 0.02 µg/ml) (P < 0.05 for both groups). The same pattern was found when changes in IL-6 serum levels of participants in rice husk (mean change = - 0.48 ± 0.11 pg/ml) and rice bran (mean change = - 0.57 ± 0.13 pg/ml) groups were compared to the control group (mean change= - 0.19 ± 0.07 pg/ml) (P < 0.05 for both groups). CONCLUSION: The results of this study showed positive effects of rice bran and rice husk powder supplementation, combined with an energy-restricted diet, on inflammatory markers among overweight and obese adults.

Cafeteria diet induces neuroplastic modifications in the nucleus accumbens mediated by microglia activation.

High-palatable and caloric foods are widely overconsumed due to hedonic mechanisms that prevail over caloric necessities leading to overeating and overweight. The nucleus accumbens (NAc) is a key brain area modulating the reinforcing effects of palatable foods and is crucially involved in the development of eating disorders. We describe that prolonged exposure to high-caloric chocolate cafeteria diet leads to overeating and overweight in mice. NAc functionality was altered in these mice, presenting structural plasticity modifications in medium spiny neurons, increased expression of neuroinflammatory factors and activated microglia, and abnormal responses after amphetamine-induced hyperlocomotion. Chronic inactivation of microglia normalized these neurobiological and behavioural alterations exclusively in mice exposed to cafeteria diet. Our data suggest that prolonged exposure to cafeteria diet produces neuroplastic and functional changes in the NAc that can modify feeding behaviour. Microglia activation and neuroinflammation play an important role in the development of these neurobiological alterations.

Which cytokine is the most related to weight loss-induced decrease in arterial stiffness in overweight and obese men?

Obesity and increased arterial stiffness are risk factors for cardiovascular disease. A well-known characteristic of obesity is the chronic low-grade inflammatory state, and it causes elevation of arterial stiffness. Weight-loss reduces arterial stiffness and inflammatory level in obese individuals. However, it is unclear which inflammatory factor is most related to weight loss-induce decreases in arterial stiffness in overweight and obese men. Thus, the aim of this study was to determine which circulating cytokine level has the most effect on decreasing arterial stiffness after lifestyle modification. Twenty overweight and obese men completed a 12-week period of lifestyle modifications (combination of aerobic exercise training and dietary modification). We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness, and circulating cytokine levels using comprehensive analysis. After the 12-week lifestyle modifications, body mass was markedly decreased. Also, baPWV and the levels of several circulating cytokines significantly decreased after the lifestyle modifications. We observed a positive correlation between changes in baPWV and circulating interleukin-6 (IL-6) levels. Furthermore, multiple liner regression analysis revealed that change in baPWV was significantly associated with that in IL-6 levels after consideration of changes in systolic blood pressure and body mass index. These results suggest that for overweight and obese men, a 12-week period of lifestyle modifications-induced a decrease in circulating cytokine levels (especially IL-6 levels), leads to decreased baPWV.

Obesity/overweight reduces the risk of active tuberculosis: a nationwide population-based cohort study in Taiwan.

BACKGROUND: Obesity affects immune function by increasing the number of T helper lymphocytes, which may reduce the risk of tuberculosis (TB) infection. However, the effect of obesity on TB development has not been extensively studied. This nationwide population-based cohort study investigated the effect of obesity on TB development in Taiwanese adults. METHODS: We included 46 028 adult participants (age ⩾18 years) from three rounds (2001, 2005 and 2009) of the Taiwan National Health Interview Survey. Obesity and overweight were defined as a body mass index (BMI) ⩾27 and 24-26.9 (kg/m2), respectively. Data on BMI and other covariates at baseline were collected by in-person interviews. Incident cases of active TB were identified from the National Health Insurance database. Multivariable logistic regression was used to estimate the associations of obesity and overweight with active TB, with adjustment for age, sex, smoking, alcohol consumption, socioeconomic status and other covariates. RESULTS: In total, 241 new cases of active TB occurred during the study period. Obesity (adjusted odds ratio [AOR], 0.43; 95% confident interval [CI], 0.28-0.67) and overweight (AOR, 0.67; 95% CI, 0.49-0.91) were associated with lower risk of incident TB, after adjusting for demographic characteristics and comorbidities. There was a linear dose-response relation of BMI with active TB incidence (AOR per unit change in BMI, 0.92; 95% CI, 0.88-0.95; P <0.001). CONCLUSION: Obesity and overweight are associated with lower risk of active TB. Future studies should investigate the underlying mechanisms and clinical and epidemiological consequences of these findings.

Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis.

Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents.

The anticancer and antiobesity effects of Mediterranean diet.

Cancers have been the leading cause of death worldwide and the prevalence of obesity is also increasing in these few decades. Interestingly, there is a direct association between cancer and obesity. Each year, more than 90,000 cancer deaths are caused by obesity or overweight. The dietary pattern in Crete, referred as the traditional Mediterranean diet, is believed to confer Crete people the low mortality rates from cancers. Nevertheless, the antiobesity effect of the Mediterranean diet is less studied. Given the causal relationship between obesity and cancer, the antiobesity effect of traditional Mediterranean diet might contribute to its anticancer effects. In this regard, we will critically review the anticancer and antiobesity effects of this diet and its dietary factors. The possible mechanisms underlying these effects will also be discussed.

Phase III, efficacy and safety study of ertugliflozin monotherapy in people with type 2 diabetes mellitus inadequately controlled with diet and exercise alone.

AIMS: To conduct a phase III study to evaluate the efficacy and safety of ertugliflozin monotherapy in people with type 2 diabetes. MATERIALS AND METHODS: This was a 52-week, double-blind, multicentre, randomized, parallel-group study with a 26-week, placebo-controlled treatment period (phase A), followed by a 26-week active-controlled treatment period (phase B) in 461 men and women, aged ≥18 years with inadequate glycaemic control (glycated haemoglobin [HbA1c] concentration 7.0% to 10.5% [53-91 mmol/mol], inclusive) despite diet and exercise. Results from phase A are reported in the present paper. The primary endpoint was the change in HbA1c from baseline to week 26. RESULTS: At week 26, the placebo-adjusted least squares mean HbA1c changes from baseline were -0.99% and -1.16% for the ertugliflozin 5 and 15 mg doses, respectively ( P < .001 for both doses). The odds of having HbA1c <7.0% (53 mmol/mol) were significantly greater in the ertugliflozin 5 and 15 mg groups compared with the placebo group. Both doses of ertugliflozin significantly lowered fasting plasma glucose and 2-hour postprandial glucose levels and body weight. The placebo-adjusted differences in changes from baseline in systolic blood pressure were not statistically significant. A higher incidence of genital mycotic infections occurred in men and women treated with ertugliflozin compared with placebo. There was no significant difference between treatments in the proportion of participants with symptomatic hypoglycaemia or adverse events associated with urinary tract infection or hypovolaemia. CONCLUSIONS: Ertugliflozin 5 and 15 mg treatment for 26 weeks provides effective glycaemic control, reduces body weight and is generally well tolerated, when used as monotherapy.