Hemodynamic Parameters in Spontaneously Hypertensive Rats with Obesity and Chemically Induced Colitis during Probiotic Therapy.

We studied the dynamics of the main hemodynamic parameters in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats with visceral obesity and chemically induced colitis (CIC) against the background of probiotic therapy. Systolic BP, HR, and body temperature were recorded over 36 days using a wireless telemetry system. During 8 days (3 days before CIC induction and until the end of the experiment) the animals were intragastrically administered a probiotic based on Lactobacillus delbrueckii D5 strain. At baseline, systolic BP was significantly higher in the SHR group, while HR and body temperature did not differ in SHR and WKY rats. On day 8 after CIC induction, systolic BP, HR, and body temperature in SHR were significantly increased in comparison with the initial values. In the group of WKY rats, all indices at the end of the experiment remained at the initial levels. Probiotic therapy in SHR, in contrast to WKY rats, did not lead to normalization of body temperature and hemodynamic disorders resulting from CIC.

Visceral obesity and sarcopenia as predictors of efficacy and hematological toxicity in patients with metastatic breast cancer treated with CDK 4/6 inhibitors.

PURPOSE: We aimed to investigate whether visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA) index are predictive for efficacy and hematological toxicity in ER + HER2-metastatic breast cancer (BC) patients who received CDK 4/6 inhibitors. METHODS: This retrospective cohort study analyzed 52 patients who were treated with CDK 4/6 inhibitors between January 2018 and February 2021. The values of VAT, SAT, SMA indices and hematological parameters were noted before the start, at the third and sixth months of this treatment. The skeletal muscle area (SMA) and adipose tissue measurements were calculated at the level of the third lumbar vertebra. A SMA-index value of <40 cm2/m2 was accepted as the threshold value for sarcopenia. RESULTS: Patients with sarcopenia had a worse progression-free survival (PFS) compared to patients without sarcopenia (19.6 vs. 9.0 months, p = 0.005). Patients with a high-VAT-index had a better PFS (20.4 vs. 9.3 months, p = 0.033). Only the baseline low-SMA- index (HR: 3.89; 95% CI: 1.35-11.25, p = 0.012) and baseline low-VAT-index (HR: 2.15; 95% CI: 1.02-4.53, p = 0.042) had significantly related to poor PFS in univariate analyses. The low-SMA-index was the only independent factor associated with poor PFS (HR: 3.99; 95% CI: 1.38-11.54, p = 0.011). No relationship was observed between body composition parameters and grade 3-4 hematological toxicity. CONCLUSION: The present study supported the significance of sarcopenia and low visceral adipose tissue as potential early indicators of poor PFS in patients treated with CDK 4/6 inhibitors.

Long-term exposure to PM1 is associated with increased prevalence of metabolic diseases: evidence from a nationwide study in 123 Chinese cities.

Exposure to particulate matter (PM) has been linked to metabolic diseases. However, the effects of PM with an aerodynamic diameter ≤ 1.0 µm (PM1) on metabolic diseases remain unclear. This study is aimed at assessing the associations of PM1 with metabolic disease risk and quantifying the concentration-response (C-R) relationship of PM1 with metabolic disease risk. A national cross-sectional study was conducted, including 12,495 middle-aged and older adults in 123 Chinese cities. The two-year average concentration of PM1 was evaluated using satellite-based spatiotemporal models. Metabolic diseases, including abdominal obesity, diabetes, hypertension, dyslipidemia, and metabolic syndrome, were identified based on physical examination, blood standard biochemistry examination, and self-reported disease histories. Generalized linear models and C-R curves were used to evaluate the associations of PM1 with metabolic diseases. A total of 12,495 participants were included in this study, with a prevalence of 45.73% for abdominal obesity, 20.22% for diabetes, 42.46% for hypertension, 41.01% for dyslipidemia, and 33.78% for metabolic syndrome. The mean ± standard deviation age of participants was 58.79 ± 13.14 years. In addition to dyslipidemia, exposure to PM1 was associated with increased risks of abdominal obesity, diabetes, hypertension, and metabolic syndrome. Each 10 µg/m3 increase in PM1 concentrations was associated with 39% (odds ratio (OR) = 1.39, 95% confidence interval (CI) 1.33, 1.46) increase in abdominal obesity, 18% (OR = 1.18, 95%CI 1.12, 1.25) increase in diabetes, 11% (OR = 1.11, 95%CI 1.06, 1.16) increase in hypertension, and 25% (OR = 1.25, 95%CI 1.19, 1.31) in metabolic syndrome, respectively. C-R curves showed that the OR values of abdominal obesity, diabetes, hypertension, and metabolic syndrome were increased gradually with the increase of PM1 concentrations. Subgroup analysis indicated that exposure to PM1 was associated with increased metabolic disease risks among participants with different lifestyles and found that solid fuel users were more susceptible to PM1 than clean fuel users. This national cross-sectional study indicated that exposure to higher PM1 might increase abdominal obesity, diabetes, hypertension, and metabolic syndrome risk, and solid fuel use might accelerate the adverse effects of PM1 on metabolic syndrome risk. Further longitudinal cohort studies are warranted to establish a causal inference between PM1 exposure and metabolic disease risk.

Analysis of Serious Weight Gain in Patients Using Alectinib for ALK-Positive Lung Cancer.

INTRODUCTION: Alectinib is a standard-of-care treatment for metastatic ALK+ NSCLC. Weight gain is an unexplored side effect reported in approximately 10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed. METHODS: Change in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle were quantified using sliceOmatic software on computed tomography images at baseline, 3 months (3M), and 1 year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with more than 10 kg weight gain were referred to Erasmus MC Obesity Center CGG for in-depth analysis (e.g., assessments of appetite, dietary habits, other lifestyle, medical and psychosocial factors, and extensive metabolic and endocrine assessments, including resting energy expenditure). RESULTS: Mean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased to 10.8 cm2 (15.0%, p = 0.003) in 3M and 35.7 cm2 (39.0%, p < 0.001) in 1Y. SAT increased to 18.8 cm2 (12.4%, p < 0.001) in 3M and 45.4 cm2 (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis (n = 4) revealed increased appetite in two patients and metabolic syndrome in all four patients. CONCLUSIONS: Alectinib may cause relevant increased sarcopenic abdominal obesity, with increases of both VAT and SAT, quickly after initiation. This may lead to many serious metabolic, physical, and mental disturbances in long-surviving patients.

Associations of long-term exposure to particulate matter with gallstone risks in Chinese adults: A large cross-sectional study.

BACKGROUND: Epidemiological evidence regarding the relation of exposure to ambient particulate matter (PM) with gallstone disease (GSD) risk remains lacking. We tested the hypothesis that long-term exposure to PM is related to the development of GSD and that dyslipidemia can mediate the effect of PM-associated GSD formation. METHODS: We extracted related information on the basis of the baseline survey of the China Multi-Ethnic Cohort Study. The exposure levels of PM (PM1, PM2.5, and PM10) were assessed by validated spatiotemporal models. The relation of exposure to ambient PM with GSD risks was analyzed by non-conditional logistic regression models. Additionally, mediation analysis was conducted to assess whether dyslipidemia was related to the relation of PM exposure with GSD risks. RESULTS: A total of 72,893 participants were included. Increased ambient PM exposure was positively associated with a higher GSD risk, with ORs (and 95% CI) of 1.17 (1.06, 1.28), 1.10 (1.05, 1.15), and 1.07 (1.04, 1.10) for every 10 µg/m3 increment in PM1, PM2.5, and PM10, separately. The association was more remarkable in males, drinkers, and central obesity participants. Dyslipidemia significantly mediated the association between PM and GSD, with mediating proportions of 5.37%, 9.13%, and 7.66% in PM1, PM2.5, and PM10, respectively. CONCLUSION: Exposure to PM may relate to the increased risk of GSD in Chinese adults, especially among males, drinkers, and central obesity participants. Dyslipidemia may partially mediate the effect of PM-associated GSD development. Our results might provide epidemiological evidence for the progression of GSD related to PM and give new insights into GSD prevention and screening priorities.

Regional urbanicity levels modify the association between ambient air pollution and prevalence of obesity: A nationwide cross-sectional survey.

Ambient air pollution exposure may increase the risk of obesity, but the population susceptibility associated with urbanicity has been insufficiently investigated. Based on a nationwide representative cross-sectional survey on 44,544 adults, high-resolution night light satellite remote sensing products, and multi-source ambient air pollution inversion data, the present study evaluated the associations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations with the prevalence of obesity and abdominal obesity. We further calculated the associations in regions with different urbanicity levels characterized by both administrative classification of urban/rural regions and night light index (NLI). We found that 10 µg/m3 increments in PM2.5 at 1-year moving average and in NO2 at 5-year moving average were associated with increased prevalence of obesity [odds ratios (OR) = 1.16 (1.14, 1.19); 1.12 (1.09, 1.15), respectively] and abdominal obesity [OR = 1.08 (1.07, 1.10); 1.07 (1.05, 1.09), respectively]. People in rural regions experienced stronger adverse effects than those in urban regions. For instance, a 10 µg/m3 increment in PM2.5 was associated with stronger odds of obesity in rural regions than in urban regions [OR = 1.27 (1.23, 1.31) vs 1.10 (1.05, 1.14), P for interaction <0.001]. In addition, lower NLI values were associated with constantly amplified associations of PM2.5 and NO2 with obesity and abdominal obesity (all P for interaction <0.001). In summary, people in less urbanized regions are more susceptible to the adverse effects of ambient air pollution on obesity, suggesting the significance of collaborative planning of urbanization development and air pollution control, especially in less urbanized regions.

Long-Term Exposure to Air Pollution and the Occurrence of Metabolic Syndrome and Its Components in Taiwan.

BACKGROUND: Metabolic syndrome (MetS), a major contributor to cardiovascular and metabolic diseases, has been linked with exposure to air pollution. However, the relationship between air pollutants and the five components of MetS [abdominal obesity, elevated triglyceride, decreased high-density lipoprotein cholesterol (HDL-C), elevated blood pressure, and elevated fasting blood glucose levels], has not been clearly described. OBJECTIVE: We examined the association between long-term exposure to air pollutants and the occurrence of MetS and its components by using a longitudinal cohort in Taiwan. METHODS: The MJ Health Research Foundation is a medical institute that conducts regular physical examinations. The development of MetS, based on a health examination and the medical history of an MJ cohort of 93,771 participants who were enrolled between 2006 and 2016 and had two or more examinations, was compared with estimated exposure to air pollutants in the year prior to health examination. The exposure levels to fine particulate matter [PM with an aerodynamic diameter of ≤2.5µm (PM2.5)] and nitrogen dioxide (NO2) in the participants' residential areas were estimated using a hybrid Kriging/land-use regression (LUR) model executed using the XGBoost algorithm and a hybrid Kriging/LUR model, respectively. Cox regression with time-dependent covariates was conducted to estimate the effects of annual air pollutant exposure on the risk of MetS and its components. RESULTS: During the average follow-up period of 3.4 y, the incidence of MetS was 38.1/1,000 person-years. After mutual adjustment and adjustments for potential covariates, the results indicated that every 10-µg/m3 increase in annual PM2.5 concentration was associated with an increased risk of abdominal obesity [adjusted hazard ratio (aHR)=1.07; 95% confidence interval (CI): 1.01, 1.14], hypertriglyceridemia (aHR=1.17; 95% CI: 1.11, 1.23), low HDL-C (aHR=1.09; 95% CI: 1.02, 1.17), hypertension (aHR=1.15; 95% CI: 1.09, 1.21), and elevated fasting blood glucose (aHR=1.15; 95% CI: 1.10, 1.20). Furthermore, PM2.5 and NO2 may increase the risk of developing MetS among people who already "have" some components of MetS. DISCUSSION: Our findings suggest that in apparently healthy adults undergoing physical examination, exposure to PM2.5 and NO2 might be associated with the occurrence of MetS and its components. https://doi.org/10.1289/EHP10611.

The mediating function of obesity on endocrine-disrupting chemicals and insulin resistance in children.

OBJECTIVES: To explore the association of endocrine-disrupting chemicals (EDCs) with insulin resistance (IR) in children as well as whether obesity played a mediation role between EDCs and IR. METHODS: In this cross-sectional study, the data of 878 subjects were included, and divided into the non-IR group (n=501) and IR group (n=377). The associations of EDC and IR, obesity, abdominal obesity were shown by restricted cubic spline (RCS). Univariate and multivariable logistic analysis were applied to explore the associations between EDCs and IR as well as EDCs and obesity, respectively. Bootstrap coefficient product was used to analyze the medication effect of obesity on EDCs and IR. RESULTS: RCS showed that increase of benzophenone-3 (BP-3) level was associated with increased risk of IR, obesity and abdominal obesity. After adjusting for confounders, BP-3>100 ng/mL was a risk factor for IR (OR=1.42, 95%CI: 1.11-1.81). In the adjusted model, we found BP-3>100 ng/mL was a risk factor for both obesity (OR=1.52, 95%CI: 1.13-2.04) and abdominal obesity (OR=1.68, 95%CI: 1.11-2.54). The indirect effect of obesity as a mediator on the relationship between BP-3 and IR was 0.038 (95%CI: 0.016-0.090) and the direct effect of obesity as a mediator on the relationship between BP-3 and IR was 0.077 (95%CI: 0.001-0.160). As for abdominal obesity, the indirect effect of it on the relationship between BP-3 and IR was 0.039 (95%CI: 0.007-0.070). CONCLUSIONS: BP-3 level might be a risk factor for IR and obesity in children, and obesity was a mediator on the relationship between BP-3 and IR in children.

Association of occupational exposure to pesticides with overweight and abdominal obesity in family farmers in southern Brazil.

The association of chronic exposure to pesticides with overweight and abdominal obesity in adult farmers was investigated. This cross-sectional study included a random sample of 122 farmers and their family members of both sexes (61% were male), living in the municipality of Farroupilha, southern Brazil. Pesticide groups and their individual compounds were self-reported and classified according to major functional and chemical classes (never used, 1-20 years, or > 20 years of use). Abdominal obesity and overweight were the outcomes of interest. A multivariate Poisson regression model was analyzed. After confounding factors were controlled, chronic use (>20 years) of insecticides (PR: 1.45; 95% CI: 1.00-2.10) and organophosphorus pesticides (PR: 1.48, 95% CI: 1.02-2.12) was associated with a higher prevalence of overweight but not abdominal obesity. Additional studies are needed to confirm our findings and clarify the specific mechanisms of these pollutants in the etiology of obesity.

Hyperuricemia Inhibition Protects SD Rats Against Fructose-Induced Obesity Hypertension Via Modulation of Inflammation and Renin-Angiotensin System in Adipose Tissue.

OBJECTIVE: The present study was aimed to reveal the relationship between uric acid and fructose-induced obesity hypertension and its mechanisms. METHODS: A rat model with obesity hypertension was induced by a high-fructose diet. In the experiment I, the rats were fed with fructose for 8 wks along with allopurinol or benzbromarone at the beginning. In the experiment II, the rats were fed with fructose for 8 wks firstly. And then, these rats were treated with allopurinol or benzbromarone for additional 6 wks. RESULTS: Fructose-fed rats showed hyperuricemia, abdominal obesity hypertension and an activation in adipose renin-angiotensin system (RAS). Also, fructose-fed rats had higher levels of proinflammatory cytokines and more macrophages infiltrating in adipose tissue. In the experiment I, allopurinol and benzbromarone significantly reduced serum uric acid at 8 wk. Adipose RAS overactivation, adipose inflammatory responses and the development of obesity hypertension were all effectively prevented by hyperuricemia inhibition. In the experiment II, 6-wk treatment with allopurinol and benzbromarone significantly decreased serum uric acid, downregulated adipose RAS, abolished adipose inflammation and improved obesity hypertension. CONCLUSION: In conclusion, urate-lowering therapy protects rats against fructose-induced obesity hypertension. The mechanisms appear to be via downregulated adipose RAS and reduced inflammation in adipose tissue.

Effects of Vitamin D Supplementation on Body Composition and Metabolic Risk Factors in Men: A Randomized Controlled Trial.

Vitamin D might play a role in metabolic processes and obesity. We therefore examined vitamin D effects on metabolic markers and obesity in a randomized controlled trial (RCT). This is a post-hoc analysis of the Graz Vitamin D&TT-RCT, a single-center, double-blind, randomized placebo-controlled trial. We included 200 healthy men with serum 25-hydroxyvitamin D (25(OH) D) levels <75 nmol/L. Subjects received 20,000 IU of vitamin D3/week (n = 100) or placebo (n = 100) for 12 weeks. Outcome measures were metabolic markers, anthropometric measures, and body composition assessed by Dual-energy X-ray absorptiometry. One-hundred and ninety-two men completed the study. We found a significant treatment effect on fasting glucose/fasting insulin ratio (-5.3 (-10.4 to -0.2), p = 0.040), whereas we observed no significant effect on the remaining outcome parameters. In subgroup analyses of men with baseline 25(OH)D levels <50 nmol/L (n = 80), we found a significant effect on waist circumference (1.6 (0.3 to 2.9) cm, p = 0.012), waist-to-hip ratio (0.019 (0.002 to 0.036), p = 0.031), total body fat (0.029 (0.004 to 0.055) %, p = 0.026), and android fat (1.18 (0.11 to 2.26) %, p = 0.010). In middle-aged healthy men, vitamin D treatment had a negative effect on insulin sensitivity. In vitamin D deficient men, vitamin D has an unfavorable effect on central obesity and body composition.

Lower HDL-cholesterol, a known marker of cardiovascular risk, was associated with depression in type 1 diabetes: a cross sectional study.

BACKGROUND: Depression, metabolic disturbances and inflammation have been linked to cardiovascular disease and mortality. Low levels of high-density lipoprotein cholesterol (HDL-cholesterol), a known marker of cardiovascular risk, have been observed in patients with major depression in psychiatric populations. Our main aim was to explore associations between depression, antidepressants, and metabolic and inflammatory variables in patients with type 1 diabetes (T1D). A secondary aim was to explore variables associated with HDL-cholesterol. METHODS: Cross-sectional design. T1D patients (n = 292, men 55%, age18-59 years, diabetes duration ≥1 year) were consecutively recruited from one specialist diabetes clinic. Depression was defined as ≥8 points for Hospital Anxiety and Depression Scale-Depression sub scale. Blood samples, anthropometrics, blood pressure, and data regarding medication and life style were collected from electronic health records. Non-parametric tests, multiple logistic and linear regression analyses were performed. RESULTS: The depression prevalence was 10 and 8% used antidepressants. Median (q1, q3) HDL-cholesterol (mmol/l) was for the depressed 1.3 (1.2, 1.5) and for the non-depressed 1.6 (1.3, 1.8), p = 0.001. HDL-cholesterol levels (per mmol/l) were negatively associated with depression (Adjusted odds ratio (AOR) 0.2, p = 0.007), and the use of antidepressants was positively associated with depression (AOR 8.1, p <  0.001). No other metabolic or inflammatory variables, or life style factors, were associated with depression when adjusted for antidepressants. Abdominal obesity was associated with antidepressants in women (AOR 4.6, p = 0.029). Decreasing HDL-cholesterol levels were associated with increasing triglyceride levels (p <  0.001), increasing high-sensitive C-reactive protein (hs-CRP) levels (p = 0.021), younger age (p <  0.001), male sex (p <  0.001), and depression (p = 0.045). CONCLUSIONS: Lower HDL-cholesterol levels, known predictors of cardiovascular disease, were associated with depression in patients with T1D. The use of antidepressants was associated with abdominal obesity in women. Depression, low-grade inflammation measured as hs-CRP, higher triglycerides, male sex, and lower age were independently associated with lower HDL-cholesterol levels.

Predictors of weight gain in a cohort of premenopausal early breast cancer patients receiving chemotherapy.

AIM: In breast cancer patients, post chemotherapy weight gain is linked with increased risk of cancer recurrence. We prospectively studied a cohort of premenopausal women receiving contemporary chemotherapy following a diagnosis of breast cancer to examine factors predicting weight increase. METHODS: Between May 2005 and January 2008, 523 patients from the Prospective Outcomes in Sporadic versus Hereditary (POSH) breast cancer study entered this sub-study comparing weight prior to chemotherapy and weight and waist/hip measurements 12-months following chemotherapy. RESULTS: Data from 380 patients were available. Mean (standard deviation [SD]) pre-treatment body mass index (BMI) was 26.3 (5.6) kg/m2; 30% women gained > 5% body weight during the study period. Lower BMI at diagnosis predicted greater subsequent post treatment weight gain (4.3% relative weight gain for those in the 1st quartile of BMI compared to 0.8% for those in the 4th quartile; r = -0.22; p < 0.001). No link to chemotherapy regimens, cigarette smoking, previous parity or chemotherapy induced amenorrhoea was noted. A total of 44% of women had central obesity (post-treatment waist measurement of ≥88 cm). CONCLUSIONS: Almost a third of premenopausal patients receiving adjuvant chemotherapy for breast cancer will gain clinically significant weight and over 40% will have central obesity 12-months following diagnosis. A greater weight gain is predicted by lower pretreatment BMI.

Impairment of primary cilia contributes to visceral adiposity of high fat diet-fed mice.

Deficiency of primary cilia formation by knockout kinesin family member 3A (Kif3a) in mature osteoblasts led to osteopenia and enhanced adipogenesis. Adipogenesis plays an important role in adipose tissue expansion by High-fat-diet (HFD) induced obesity. Whether primary cilia participate in high-fat-diet induced adiposity remains unclear. In this study, we found that the number and length of primary cilia and expression levels of KIF3A and intraflagellar transport 88 homolog (IFT88) mRNA and proteins reached peak on the day 3 of adipogenesis, followed by a decrease to reach low basal expression levels at day 9 when differentiated to lipid accumulating adipocytes in VAT-SVFs derived from lean mice. The number of primary cilia was reduced by shRNA and chemical methods, leading to elevated transcripts of Pparγ, Cebp-α, Srebp-1, and Fasn and protein levels of PPARγ and FASN. Similar to the proadipogenic effect by the inhibition of primary cilia formation in control VAT-SVFs, HFD caused severe reduction of primary cilia formation and enhancement of adipogenesis in VAT-SVFs cultures. Flow cytometry analysis revealed percentage of G2/M phase cells and the protein expression of Cyclin A2 and CDK2 increased in control VAT-SVFs by knockdown of primary cilia with shRNA or chemical methods and HFD induced obese VAT-SVFs. In conclusion, the expression of primary cilia was in reverse correlation with adipogenic differentiation. HFD caused severe defects of primary cilia in VAT-SVFs, leading to adipose tissue expansion by enhancement of adipogenesis through promoting cell cycle re-entry at the early stage of adipogenesis.

Immune Response to Native Lipoproteins Induces Visceral Obesity and Aortic Wall Injury in Rats: The Role of Testosterone.

OBJECTIVES: The underlying mechanism of atherosclerosis and visceral obesity remains unknown.The purpose of this study was to test the hypothesis that atherosclerosis and visceral obesity are caused by an immune response to native plasma lipoproteins, and the atherogenic and adipogenic effects of the antibodies to native lipoproteins stem from the androgen deficiency that is created. METHODS: Wistar rats were immunized with native human (nh) low-density (LDL) or high-density lipoproteins (HDL). Visceral fat, aortic wall structure, and testosterone levels were studied. RESULTS: Immunization with nhLDL or nhHDL induced in rats increased visceral abdominal fat and perivascular adipose tissue volume, the appearance of epicardial fat, and atherosclerosis-like changes in the aortic wall: accumulation of leucocytes, destruction of the intima, and disruption of the media structure. Immunized rats produced antibodies to native plasma lipoproteins, while there was no difference between immunized and adjuvant-injected rats with regard to the level of antibodies to oxidized LDL. The immune response to nhHDL caused testosterone disturbances, but it is not associated with visceral obesity and atherosclerosis. CONCLUSION: The immune response to native lipoproteins is atherogenic and adipogenic and testosterone is not involved in the atherogenic and adipogenic effects of antibodies to lipoproteins.

Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs.

AIM: We have recently established a novel swine model for studies of atherosclerosis using MicrominipigsTM (µMPs) fed a high-fat/high-cholesterol diet (HcD). Using this swine model, we re-evaluated the effects of dietary cholic acid (CA) on serum lipid profile, atherosclerosis and hepatic injuries. METHODS: The µMPs were fed HcD supplemented with 0.7% CA (HcD＋CA) for eight weeks, and the effect of CA on serum lipoprotein levels, expression of oxidative stress markers, adiposity and lesion formation in the aorta, liver, and other organs was investigated. RESULTS: The HcD＋CA-fed group exhibited more visceral adiposity, progression of atherosclerosis and higher serum levels of oxidative stress markers than the HcD-fed group, even though they showed similar serum lipid levels. The liver demonstrated increased lipid accumulation, higher expression of oxidative stress markers, accelerated activation of foamy Kupffer cells and stellate cells, and increased hepatocyte apoptosis, indicating non-alcoholic fatty liver disease (NAFLD). Intriguingly, foamy macrophage mobilization was observed in various organs, including the reticuloendothelial system, pulmonary capillary vessels and skin very often in HcD＋CA-fed µMPs. CONCLUSION: To our knowledge, this is the first large animal model, in which visceral obesity, NAFLD and atherosclerosis are concomitantly induced by dietary manipulation. These data suggest the detrimental effects of CA, potentially through local and systemic activation of oxidative stress-induced signaling to macrophage mobilization, on the acceleration of visceral adiposity, atherosclerosis and NAFLD.

Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1ß mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1ß levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity.

Effects of polyphenol compounds melanin on NAFLD/NASH prevention.

BACKGROUND: One of the pathogenic mechanisms of the progression non-alcoholic liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is the accumulation of reactive oxygen species (ROS). So, antioxidant therapy is necessary for successful treatment of the liver injury. We have paid attention to melanin produced by yeast Nadsoniella nigra strain X-1 as novel antioxidant and anti-inflammatory agents with low toxicity. In current study we aimed to investigate the preventive effect of melanin on the monosodium glutamate (MSG) induced NAFLD model in rats. METHODS: The study was carried out on 45 Wistar rats that were divided into 3 groups: intact, MSG- and MSG+melanin groups (n=15 in each group). Newborn rats of MSG- and MSG+melanin groups were administered with MSG (4mg/g, 8µl/g, subcutaneously) at 2nd-10th days of life. Since the age of 1 month, rats of MSG-group were treated with water (0.25ml/100g), rats of MSG+melanin groups-with melanin (1mg/kg) dissolved in water (0.25ml/100g). INTRODUCTION: had been performed intermittently (two-week courses alternated with two-week breaks) for 3 months. In 4-month rats anthropometrical parameters and visceral adipose tissue (VAT) mass were estimated. To assess morphological changes in liver we used NAS (NAFLD activity score). The content of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-12Bp40, interferon (INF)-γ) and anti-inflammatory cytokines (IL-4, IL-10, tumor growth factor (TGF)-ß) were measured by ELISA. RESULTS: We found significantly lower total score (1.0±0.19 vs 3.33±0.36, p<0.001), degree of steatosis (0.73±0.18 vs 1.80±0.17, p<0.001) and manifestation of lobular inflammation (0.27±0.11 vs 1.20±0.17, p<0.001) due to NAFLD activity score in MSG+melanin group compared to MSG-obesity. NASH we confirmed only in 33.3% of rats with MSG-obesity that was significantly higher than after melanin (6.7%) administration (p=0.033). Melanin administration reduce amount of visceral fat on 44.5% (p<0.001) as compared to MSG-obesity group. Melanin reduced the content of IL-1ß in rat serum and restored the level of anti-inflammatory cytokines (IL-10, TGF-ß) to the control values. CONCLUSION: Thus, the administration of melanin can prevent development of NAFLD/NASH in rats with MSG-induced obesity and can be considered as possible novel therapeutic agents but further studies to confirm its action needed.

Possible influence of the environmental pollutant bisphenol A on the cardiometabolic risk factors.

Bisphenol A (BPA) is a ubiquitous environmental pollutant which is often associated with various health issues. In this study 103 healthy female volunteers in reproductive age from Serbian north province Vojvodina were enrolled and examined for the BPA exposure in the urine samples after 12 h of fasting. BPA was found in 35.92 % (37/103) of subjects. Statistically significant increment in waist circumference (p = 0.045) and waist-to-height ratio (p = 0.037) was observed among the BPA positive women in comparison with the women who had the same energetic balance and had not been exposed to BPA. Linear correlation was obtained between the BPA concentration in urine samples and body mass index (r2 = 0.35, p = 0.003) waist circumference (r2 = 0.21, p = 0.02) and waist-to-height ratio (r2 = 0.25, p = 0.01) among the obese. High energetic intake and reduced physical activity additionally pronounced BPA positive association with obesity. No statistically significant difference was observed in triglycerides, HDL and LDL cholesterol levels between the BPA exposed and BPA non-exposed female volunteers.

[PSYCHOEDUCATIONAL PROGRAM AS A WAY OF CORRECTING MOTIVATIONAL COMPONENTS IN PATIENTS WITH PARANOID SCHIZOPHRENIA WITH ABDOMINAL OBESITY].

The aim of the study was to investigate the influence of motivational and targeted psychoeducational programs designed for patients with paranoid schizophrenia with abdominal obesity. We observed 34 women aged 18-42 with continuous-flow type paranoid schizophrenia. All patients had a concomitant abdominal obesity, which developed secondarily after long-term administration of second generation antipsychotic medications (at least 1 year). Based on clinical-psychopathological and psychometric methods of assessment and on the analysis of Treatment Satisfaction Questionnaire we have developed modules for psychoeducational programs. Based on the results of the treatment we conclude that the application of psychoeducational programs is an effective component of complex treatment of patients with paranoid schizophrenia. Abdominal obesity should be regarded as an important and the main side effect of long-term therapy with atypical antipsychotic medications. It has a marked negative effect on subjective assessment of patients and decreases the level of their mental and social adaptation. This factor should be the basis for the formation of re-socialization and compliance-oriented actions.