Association between urinary nickel with obesity status in adults: A cross-sectional study.

Objectives: The prevalence of obesity is on the rise and is connected to numerous factors. However, the relationship between obesity and nickel has never been investigated. Our study aimed to explore the association between urinary nickel and obesity Status in adults. Methods: From the 2017-2018 National Health and Nutrition Examination Surveys (NHANES), 1,705 participants ≥18 years of age were enrolled. To explore further the relationship among urinary nickel, body mass index (BMI), and waist circumference(WC), Weighted multivariate linear regression analyses and further subgroup analyzes were conducted. Results: Urinary nickel does not correlate with BMI level but positively correlates with WC. In the subgroup analyzed according to sex, Urinary nickel has a positive correlation with BMI and WC in males but has a negative correlation in females. Secondary stratification analysis according to sex and race, Urinary nickel positively correlates with BMI in White males. It also positively correlates with WC in both White and Black males. Conclusions: A correlation was found between urinary nickel levels and BMI and WC in adult males. Adult men, especially those already obese, may need to reduce nickel exposure.

Role of insulin resistance and the gut microbiome on urine oxalate excretion in ob/ob mice.

Ob/ob mice have recently emerged as a model for obesity-related hyperoxaluria as they are obese and excrete more urine oxalate compared to wild type mice. Ob/ob mice are deficient of leptin and develop obesity with hyperphagia and hyperinsulinemia. We hypothesized that insulin resistance and the gut microbiome contribute to hyperoxaluria in ob/ob mice. We developed a new liquid chromatography-mass spectrometry assay for urine oxalate and first compared urine oxalate excretion in ob/ob mice before and after ablation of intestinal bacteria with a standard antibiotic cocktail. We then compared urine oxalate excretion in ob/ob mice before and after leptin replacement or pioglitazone treatment, two maneuvers that reduce insulin resistance in ob/ob mice. Ob/ob mice excreted more oxalate into the urine in a 24-h period compared to wild type mice, but antibiotic, leptin, or pioglitazone treatment did not change urine oxalate excretion in ob/ob mice. Unexpectedly, we found that when food intake was carefully matched between ob/ob and wild type mice, the amount of 24-h urine oxalate excretion did not differ between the two mouse strains, suggesting that ob/ob mice excrete more urine oxalate because of hyperphagia. Since the level of urine oxalate excretion in wild type mice in our study was higher than those reported in prior studies, future work will be needed to standardize the measurement of urine oxalate and to define the range of urine oxalate excretion in wild type mice so that accurate and valid comparisons can be made between wild type mice and ob/ob mice or other mouse models.

Reduction of oxidative stress on DNA and RNA in obese patients after Roux-en-Y gastric bypass surgery-An observational cohort study of changes in urinary markers.

Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and after surgery were compared as estimates of the total 24-hour excretion, using a model based on glomerular filtration rate (calculated from cystatin C, age, height and weight), plasma- and urinary creatinine. The excretion of 8-oxodG increased in the first months after RYGB. For 8-oxoGuo, a gradual decrease was seen. Two years after RYGB and a mean weight loss of 35 kg, decreased hyperglycemia and insulin resistance, excretion levels of both markers were reduced by approximately 12% (P < 0.001). For both markers, mean excretion levels were about 30% lower in the female subgroup (P < 0.0001). Also, in this subgroup, excretion of 8-oxodG was significantly lower in patients with than without diabetes. We conclude, that oxidative damage to nucleic acids, reflected in the excretion of 8-oxodG and 8-oxoGuo, had decreased significantly two years after RYGB-indicating that reduced oxidative stress could be contributing to the many long-term benefits of RYGB-surgery in obesity and type 2 diabetes.

Identification of pathognomonic purine synthesis biomarkers by metabolomic profiling of adolescents with obesity and type 2 diabetes.

The incidence of type 2 diabetes is increasing more rapidly in adolescents than in any other age group. We identified and compared metabolite signatures in obese children with type 2 diabetes (T2D), obese children without diabetes (OB), and healthy, age- and gender-matched normal weight controls (NW) by measuring 273 analytes in fasting plasma and 24-hour urine samples from 90 subjects by targeted LC-MS/MS. Diabetic subjects were within 2 years of diagnosis in an attempt to capture early-stage disease prior to declining renal function. We found 22 urine metabolites that were uniquely associated with T2D when compared to OB and NW groups. The metabolites most significantly elevated in T2D youth included members of the betaine pathway, nucleic acid metabolism, and branched-chain amino acids (BCAAs) and their catabolites. Notably, the metabolite pattern in OB and T2D groups differed between urine and plasma, suggesting that urinary BCAAs and their intermediates behaved as a more specific biomarker for T2D, while plasma BCAAs associated with the obese, insulin resistant state independent of diabetes status. Correlative analysis of metabolites in the T2D signature indicated that betaine metabolites, BCAAs, and aromatic amino acids were associated with hyperglycemia, but BCAA acylglycine derivatives and nucleic acid metabolites were linked to insulin resistance. Of major interest, we found that urine levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) were increased in diabetic youth, identifying urine SAICA-riboside as a potential biomarker for T2D.

Cross talk between Hsp72, HMGB1 and RAGE/ERK1/2 signaling in the pathogenesis of bronchial asthma in obese patients.

BACKGROUND: The incidence of obesity-related asthma has shown a remarkable increase. OBJECTIVES: We aimed to explore the role of heat shock protein 72 (Hsp72) and receptor for advanced glycation end products (RAGE) axis with its downstream signaling in the pathogenesis of obesity-related asthma. METHODS: We enrolled a total of 55 subjects and divided them into three groups. Groups I and II included healthy, normal weight (n = 15) and obese (n = 15) subjects, respectively. Twenty-five obese asthmatics (group III) were subdivided into group IIIa (10 patients with mild to moderate asthma) and group IIIb (15 patients with severe asthma). High mobility group box 1 (HMGB1), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and urinary Hsp72 were immunoassayed. Hydrogen peroxide (H2O2) and free fatty acids (FFAs) levels were photometrically measured. RAGE mRNA expression was relatively quantified by real-time PCR. RESULTS: We found significant elevations of serum HMGB1, IL-8, MCP1, ERK1/2, FFAs, and H2O2 levels as well as urinary Hsp72 levels in obese subjects compared to healthy control. These were more evident in patients with severe asthma (group IIIb). Multivariate regression analysis identified Hsp72 and ERK1/2 as independent predictors of bronchial asthma severity. Receiver operating characteristic (ROC) curve analysis revealed that areas under the curve (AUC) for Hsp72 and ERK1/2 were 0.991 and 0.981, respectively, which denotes a strong predictive value for identifying the severity of bronchial asthma in obese patients. CONCLUSION: The current study highlights the role of Hsp72 and HMGB1/RAGE/ERK1/2 signaling cascade in the pathogenesis of bronchial asthma and its link to obesity, which could be reflected on monitoring, severity grading, and management of this disease.

Rapid Progression of Knee Pain and Osteoarthritis Biomarkers Greatest for Patients with Combined Obesity and Depression: Data from the Osteoarthritis Initiative.

OBJECTIVE: To compare the progression of biochemical biomarkers of osteoarthritis (OA), knee pain, and function between nonobese patients (NON), obese patients without depression (OBESE), and obese patients with comorbid depression (O + D). DESIGN: Utilizing the FNIH OA Biomarkers Consortium dataset, we categorized knee OA patients into NON, OBESE, and O + D groups based on body mass index and Center for Epidemiological Studies-Depression (CES-D) scores. Subjective symptoms (Knee injury and Osteoarthritis Outcome Score Quality of Life subscale (KOOS QOL), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function scores, and the Short Form-12 (SF-12) Physical Component Score [PCS]) and objective measures of cartilage degradation and bone remodeling (urinary CTXII and CTXIα) were compared among groups at baseline and 2-year follow-up. RESULTS: Of the 600 patients, 282 (47%) were NON, 285 (47.5%) OBESE, and 33 (5.5%) O + D. The O + D group had significantly worse pain and function both at baseline and 2-year follow-up (P < 0.001 for all comparisons) as evidenced by self-reported measures on KOOS QOL, WOMAC Pain, WOMAC Physical Function, and SF-12 PCS. The O + D group also demonstrated significant increases in CTXII (P = 0.01) and CTXIα (P = 0.005), whereas the NON and OBESE groups did not. CONCLUSIONS: The combination of inferior knee pain, physical function, and significantly greater increases in biomarkers of cartilage degradation and bony remodelling suggest a more rapid progression for obese OA patients with comorbid depression. The link between systemic disease, inflammatory burden, and progressive cartilage degradation is in line with increasing concerns about a degenerative synovial environment in early osteoarthritic knees that progress to treatment failure with biologic restoration procedures.

Gender-Related Differences on Polyamine Metabolome in Liquid Biopsies by a Simple and Sensitive Two-Step Liquid-Liquid Extraction and LC-MS/MS.

Polyamines are involved in the regulation of many cellular functions and are promising biomarkers of numerous physiological conditions. Since the concentrations of these compounds in biological fluids are low, sample extraction is one of the most critical steps of their analysis. Here, we developed a comprehensive, sensitive, robust, and high-throughput LC-MS/MS stable-isotope dilution method for the simultaneous determination of 19 metabolites related to polyamine metabolism, including polyamines, acetylated and diacetylated polyamines, precursors, and catabolites from liquid biopsies. The sample extraction was optimized to remove interfering compounds and to reduce matrix effects, thus being useful for large clinical studies. The method consists of two-step liquid-liquid extraction with a Folch extraction and ethyl acetate partitioning combined with dansyl chloride derivatization. The developed method was applied to a small gender-related trial concerning human serum and urine samples from 40 obese subjects. Sex differences were found for cadaverine, putrescine, 1,3-diaminopropane, γ-aminobutyric acid, N8-acetylspermidine, and N-acetylcadaverine in urine; N1-acetylspermine in serum; and spermine in both serum and urine. The results demonstrate that the developed method can be used to analyze biological samples for the study of polyamine metabolism and its association with human diseases.

A Proteomics-Based Approach Reveals Differential Regulation of Urine Proteins between Metabolically Healthy and Unhealthy Obese Patients.

Metabolic dysfunction associated with obesity threatens to inundate health care resources by increasing the incidences of obesity-related diseases. The aim of the present study was to investigate the changes in the urinary proteome of 18 individuals classified into metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) patients. Proteome analysis was performed using the two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Upon analysis, a total of 54 proteins were found to be affected with ≥1.5-fold change (ANOVA, p ≤ 0.05), of which 44 proteins were upregulated and 10 proteins were downregulated. These differentially abundant proteins were related to nuclear factor κB (NF-κB) and p38 mitogen-activated protein (MAP) kinase pathways and were involved in cellular compromise, inflammatory response, and cancer. Proteins involved in inflammation (fibrinogen alpha (FIBA), serotransferrin (TRFE, and kininogen-1 (KNG1)) and insulin resistance (ADP-ribosylation factor (ARF)-like protein 15 (ARL15) and retinol-binding protein 4 (RET4)) were found to be significantly increased in the urine samples of MUHO compared to MHO patients. Investigating the effects of obesity on urinary proteins can help in developing efficient diagnostic procedures for early detection and prevention of obesity-related complications.

Reduction in FSH Throughout the Menstrual Cycle After Omega-3 Fatty Acid Supplementation in Young Normal Weight but not Obese Women.

Dietary fish oil restores ovarian function in subfertile rats, which is thought to be associated with decreased transcription of follicle-stimulating hormone (FSH) ß-subunit. We have previously demonstrated a reduction in early follicular serum FSH levels in normal weight but not obese women after treatment with omega-3 polyunsaturated fatty acids (PUFA). Herein, we report the effect of supplementation with omega-3 PUFA on urinary reproductive hormones across the whole menstrual cycle. This interventional study included 17 eumenorrheic women, aged 24-41 years. One month of daily morning urine was collected before and after 1 month of omega-3 PUFA supplementation with 4 g of eicosapentaenoic acid and docosahexaenoic acid daily. Measurements included urinary FSH, luteinizing hormone (LH) and estrogen and progesterone metabolites, plasma fatty acid composition, and markers of endoplasmic reticulum stress. Compliance with dietary supplementation was verified by significantly reduced ratios of omega-6 to omega-3 PUFA for all subjects after treatment (P < .01). After 1 month of omega-3 PUFA supplementation, urinary FSH was significantly decreased in normal weight, but not obese women, in both follicular and luteal phases (-28.4% and -12.6%, respectively, both P = .04). No significant changes were seen in LH or sex steroids for either weight group. The selective and specific decrease in FSH suggests that omega-3 PUFA supplementation merits further investigation in normal weight women with decreased fertility and/or diminished ovarian reserve.

Weight management telehealth intervention for overweight and obese rural cardiac rehabilitation participants: A randomised trial.

AIMS AND OBJECTIVES: To determine whether a weight management intervention (WMI) plus cardiac rehabilitation (CR) compared to CR alone improves outcomes for overweight and obese cardiac revascularisation patients. BACKGROUND: Despite participating in cardiac rehabilitation (CR), few cardiac patients lose enough weight to achieve clinically significant cardiovascular disease risk reduction. DESIGN: A randomised controlled design was used with measurements at baseline, 4 and 6 months, guided by the CONSORT checklist, see Supporting Information File S1. Adults who had undergone either coronary artery bypass surgery (CABS) or percutaneous coronary intervention (PCI) and participated in a rural CR programmes were recruited. Subjects were randomised to a 12-week telehealth WMI or control group. The primary outcome was weight loss. Secondary outcomes included physical activity, patient activation, perceived self-efficacy and use of weight management behaviours. RESULTS: A total of 43 subjects participated, with a mean age of 63 (±9.3) years. The WMI group had significantly more weight loss averaged across the 4 and 6 months of 13.8 (±2.8) pounds compared to the control group [mean = 7.8 (±2.2) pounds]. There were no significant differences in physical activity (activity counts or daily minutes in moderate or more intense activity). The WMI group had significantly higher levels of patient activation. They also had significantly higher total scores on the Diet and Exercise Self-Management survey, and subscales that included self-efficacy for specific eating habits and managing diet behaviour. CONCLUSIONS: Findings demonstrated the usefulness and feasibility of using telehealth delivery of the WMI for cardiac rehabilitation participants in rural communities to improve weight management outcomes. RELEVANCE TO PRACTICE: Study findings underscore the opportunity to further improve weight loss of overweight and obese cardiac participants using a weight management intervention to augment CR participation.

Association between exposure to a mixture of phenols, pesticides, and phthalates and obesity: Comparison of three statistical models.

BACKGROUND: The evaluation of the chemical impact on human health is usually constrained to the analysis of the health effects of exposure to a single chemical or a group of similar chemicals at one time. The effects of chemical mixtures are seldom analyzed. In this study, we applied three statistical models to assess the association between the exposure to a mixture of seven xenobiotics (three phthalate metabolites, two phenols, and two pesticides) and obesity. METHODS: Urinary levels of environmental phenols, pesticides, and phthalate metabolites were measured in adults who participated in the U.S.-based National Health and Nutrition Examination Survey (NHANES) from 2013 to 2014. Body examination was conducted to determine obesity. We fitted multivariable models, using generalized linear (here both logistic and linear) regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models to estimate the association between chemical exposures and obesity. RESULTS: Of 1269 individuals included in our final analysis, 38.5% had general obesity and 58.0% had abdominal obesity. In the logistic regression model established for each single chemical, bisphenol S (BPS), mono (carboxyoctyl) phthalate (MCOP), and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) were associated with both general and abdominal obesity (fourth vs. first quartile). In linear regression, MCOP was associated with BMI and waist circumference. In WQS regression analysis, the WQS index was significantly associated with both general obesity (OR = 1.63, 95% CI: 1.21-2.20) and abdominal obesity (OR = 1.66, 95% CI: 1.18-2.34). MCOP, bisphenol A (BPA), bisphenol S (BPS), and mono ethyl phthalate (MEP) were the most heavily weighing chemicals. In BKMR analysis, the overall effect of mixture was significantly associated with general obesity when all the chemicals were at their 60th percentile or above it, compared to all of them at their 50th percentile. MCOP, BPA, and BPS showed positive trends. By contrast, MECPP showed a flat and modest inverse trend. CONCLUSION: When comparing results from these three models, MCOP, BPA, and BPS were identified as the most important factors associated with obesity. We recommend estimating the joint effects of chemical mixtures by applying diverse statistical methods and interpreting their results together, considering their advantages and disadvantages.

Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury.

AIM: Metabolic acidosis occurs due to insufficient urinary ammonium excretion as chronic kidney disease (CKD) advances. Because obese subjects tend to have excessive consumption of protein and sodium chloride, they are prone to chronic acid loading and may therefore be predisposed to acid-induced kidney injury. We investigated the involvement of obesity in ammoniagenesis within damaged kidneys. METHODS: In the clinical study, urinary ammonium excretion was compared between 13 normal-weight and 15 overweight/obese CKD outpatients whose creatinine clearance was higher than 25 mL/min. For animal experiments, NH4 Cl was loaded to KKAy/TaJcl (KKAy), a metabolic syndrome model, and control BALB/c mice for 20 weeks. Kidney injury was evaluated through histological analysis and the expression of proinflammatory markers. RESULTS: Urinary ammonium excretion was lower in overweight/obese patients than in normal-weight patients, while intakes of protein and sodium chloride were higher in overweight/obese patients, implying that subclinical metabolic acidosis occurs in overweight/obese patients. The increase in urinary ammonium excretion induced by NH4 Cl loading was attenuated in KKAy mice after 16 weeks, whereas the increase was maintained in BALB/c mice throughout the study period. Histological study and real-time polymerase chain reaction analysis showed proximal tubular injury and enhanced expression levels of neutrophil gelatinase-associated lipocalin (NGAL) protein and messenger RNA, respectively, in KKAy mice but not in BALB/c mice. Finally, urinary NGAL concentration was higher in overweight/obese patients than in normal-weight patients in the early stage of CKD. CONCLUSION: Obesity could facilitate the induction of subclinical metabolic acidosis and acid accumulation in the kidney, which may potentially exacerbate kidney injury in CKD patients.

Are there any new reliable markers to detect renal injury in obese children?

AIM: The aim of this study was to examine the serum and urine levels of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), matrix metalloproteinase-9 (MMP-9), and serum Cystatin-C to determine the renal effect of obesity in obese children. METHODS: Seventy-two obese and 35 non-obese healthy children were included in this study. Blood pressure (BP) was evaluated with office measurement. Creatinine, cystatin C, lipids, fasting glucose, and insulin levels were measured, and homeostasis model assessment -insulin resistance (HOMA-IR) was calculated. The urine albumin/creatinine ratio was calculated. The serum and urine KIM-1, NGAL, OPN, and MMP-9 levels were measured. RESULTS: Serum cystatin-C, triglyceride, and homeostasis model assessment-insulin resistance (HOMA-IR) index were found to be significantly higher in the obese group (p = .0001), and high-density lipoprotein (HDL) cholesterol was found to be significantly lower (p = .019) in the obese group. No significant differences were found in serum KIM-1, NGAL, OPN or MMP-9 levels between groups (p > .05). No significant differences were found in urine KIM-1 and MMP-9 levels (p > .05), Urine NGAL, and OPN levels were found significantly higher in obese groups (p < .05). CONCLUSIONS: According to our results, although serum KIM-1, NGAL, OPN, MMP-9, and urine MMP-9, urine KIM-1 do not appear to be ideal markers to evaluate renal injury in the early period of obesity, the serum levels of cystatin C and urine NGAL, urine OPN can be used as a good marker for assessing the renal effect of obesity which can lead end stage renal disease in pediatric population.

Hydrolyzed proteins from herring and salmon rest raw material contain peptide motifs with angiotensin-I converting enzyme inhibitors and resulted in lower urine concentrations of protein, cystatin C and glucose when fed to obese Zucker fa/fa rats.

The use of angiotensin-I converting enzyme (ACE) inhibitors is a common strategy for treating kidney disease. Several amino acid sequences with ACE inhibiting activity are identified in filet and rest raw material from various species of fish, and fish protein hydrolysates could be of interest for possible treatment or prevention of kidney disease. Therefore, we hypothesized that protein hydrolysates from rest raw material from herring and salmon contained ACE inhibiting motifs, and could beneficially affect typical markers for kidney function in an obesity rat model prone to developing renal failure. We identified 81 and 49 peptide sequences with known ACE inhibiting activity in herring and salmon protein hydrolysates from rest raw material, respectively. To investigate the effects of fish protein hydrolysates on markers of kidney function, obese Zucker fa/fa rats consumed diets with 25% of protein from herring (HER) or salmon (SAL) protein hydrolysate from rest raw material and 75% of protein from casein/whey, or 100% protein from casein/whey (CAS) for 4 weeks. Rats fed HER or SAL diets had lower urine concentrations (relative to creatinine) of protein, cystatin C and glucose when compared to rats fed CAS diets, with no differences between groups for serum concentrations of protein, creatinine and cystatin C. To conclude, protein hydrolysates from herring and salmon rest raw material contained several peptide sequences with known ACE inhibiting activities, and resulted in lower urine concentrations of proteins, cystatin C and glucose when fed to obese Zucker rats.

Gender-specific differences of interaction between cadmium exposure and obesity on prediabetes in the NHANES 2007-2012 population.

PURPOSE: Data from National Health and Nutrition Examination Survey (NHANES) for the years 2007-2012 were used to evaluate the interactions of cadmium (Cd) exposure with being overweight/obesity on the risk of prediabetes among adults 20 years older. METHODS: A total of 3552 subjects were included in the analysis. Urinary cadmium levels (UCd) was used as a biomarker for long-term exposure to Cd. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). RESULTS: Following covariates adjustments, we found significant associations of UCd with higher prediabetes prevalence, and this association was more apparent in males (Q4 vs Q1: OR = 1.95, 95%CI: 1.34-2.84); while overweight/obesity was associated with prediabetes both in males and in females. Additionally, there was a significant interaction between Cd exposure and being overweight/obesity on prediabetes risk among males (RERI = 1.18, 95% CI: 0.42-1.93; AP = 0.35, 95% CI: 0.12-0.58; S = 2.00, 95% CI: 0.92-4.34). CONCLUSIONS: Our results suggest that being overweight/obesity may substantially amplify the adverse effects of long-term cadmium exposure on prediabetes risk, and this interaction is more severe in male adults. Further studies are needed to confirm these findings.

Adiponectin gene polymorphisms and obesity increase the susceptibility to arsenic-related renal cell carcinoma.

Our recent study found that high urinary total arsenic levels were associated with renal cell carcinoma (RCC). Recent studies demonstrated that low circulating adiponectin was related to RCC. The aim of the present study was to explore the relationship between adiponectin gene (ADIPOQ) polymorphisms and RCC and investigate whether individuals with an ADIPOQ risk genotype, obesity, and high urinary total arsenic levels have a modified odds ratio (OR) of RCC. A total of 389 RCC patients and 389 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Image-guided biopsy or surgical resection of renal tumors was performed to pathologically verify RCC. Genomic DNA was used to examine the genotypes of the ADIPOQ rs182052, ADIPOQ rs2241766, ADIPOQ rs1501299, and ADIPOQ rs1063539 SNPs by PCR-RFLP. HPLC-HG-AAS was used to measure the concentrations of urinary arsenic species. Participants with the ADIPOQ rs182052 G/A+A/A genotype had a significantly higher OR of RCC compared with those with the ADIPOQ rs182052 G/G genotype. The OR (95% confidence interval [CI]) was 1.70 (1.23-2.36). The OR of RCC for the combined effect of high urinary total arsenic levels and obesity, which was dose-dependent, in individuals with the ADIPOQ rs182052 G/A+A/A genotype was 9.33 (3.85-22.62). The present study found significant combined effects of obesity and the ADIPOQ rs182052 G/A+A/A genotype on the arsenic-related risk of RCC in a population with low arsenic exposure. Arsenic exposure, obesity, and the ADIPOQ rs182052 polymorphism could be predictors of a higher OR of RCC.

Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in calcium stone formers / Influência do estado nutricional e dos parâmetros laboratoriais e dietéticos sobre a excreção urinária ácida em pacientes portadores de litíase cálcica

ABSTRACT Introduction: Obesity and Metabolic Syndrome (MS) are associated with low urinary pH and represent risk factors for nephrolithiasis, especially composed by uric acid. Acidogenic diets may also contribute to a reduction of urinary pH. Propensity for calcium oxalate precipitation has been shown to be higher with increasing features of the MS. Objective: A retrospective evaluation of anthropometric and body composition parameters, MS criteria and the dietary patterns of overweight and obese calcium stone formers and their impact upon urinary pH and other lithogenic parameters was performed. Methods: Data regarding anthropometry, body composition, serum and urinary parameters and 3-days dietary records were obtained from medical records of 102(34M/68F) calcium stone formers. Results: A negative correlation was found between urinary pH, waist circumference and serum uric acid levels (males). The endogenous production of organic acids (OA) was positively correlated with triglycerides levels and number of features of MS (males), and with glucose, uric acid and triglycerides serum levels, and number of features of MS (females). No significant correlations were detected between Net Acid Excretion (NAE) or Potential Renal Acid Load of the diet with any of the assessed parameters. A multivariate analysis showed a negative association between OA and urinary pH. Conclusion: The endogenous production of OA and not an acidogenic diet were found to be independently predictive factors for lower urinary pH levels in calcium stone formers. Hypercalciuric and/or hyperuricosuric patients presented higher OA levels and lower levels of urinary pH.

RESUMO Introdução: A obesidade e a Síndrome Metabólica (SM) se associam a pH urinário ácido e representam fatores de risco para litíase renal, especialmente a úrica. Dietas acidogênicas também podem contribuir para a redução do pH urinário. Já foi demonstrado maior risco de precipitação de oxalato de cálcio em proporção aos critérios de SM. Objetivo: Avaliar retrospectivamente o impacto de parâmetros antropométricos, composição corporal, critérios de SM e padrão alimentar sobre o pH urinário e outros parâmetros litogênicos em pacientes com sobrepeso e obesos com litíase cálcica. Métodos: Foram coletados dados de antropometria, composição corporal, exames séricos e urinários, e registros alimentares (3 dias) de 102 (34M/68F) pacientes com litíase cálcica. Resultados: O pH urinário se correlacionou negativamente com a circunferência da cintura e ácido úrico sérico (homens). A produção endógena de ácidos orgânicos (AO) se correlacionou positivamente com os triglicérides séricos e o número de critérios de SM (homens), e com glicemia, ácido úrico, triglicérides e número de critérios para SM (mulheres). Não se observaram correlações significantes entre a excreção renal líquida de ácidos (NAE) e o potencial de carga ácida renal (PRAL) da dieta com nenhum dos parâmetros avaliados. Na análise de regressão multivariada, os AO apresentaram associação negativa significante com o pH urinário. Conclusão: A produção endógena de AO, e não um padrão de dieta acidogênica, foi o fator determinante independente para menores níveis de pH urinário em pacientes com litíase cálcica. Pacientes com hipercalciúria e/ou hiperuricosúria apresentaram maiores valores de AO e menores de pH urinário.

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients.

PURPOSE: Benign prostatic hyperplasia (BPH) is strongly associated with obesity and prostatic tissue inflammation, but the molecular underpinning of this relationship is not known. Here, we examined the association between urine levels of chemokines/adipokines with histological markers of prostate inflammation, obesity, and lower urinary tract symptoms LUTS in BPH patients. METHODS: Frozen urine specimens from 207 BPH/LUTS patients enrolled in Nashville Men's Health Study were sent for blinded analysis of 11 analytes, namely sIL-1RA, CXC chemokines (CXCL-1, CXCL-8, CXCL-10), CC chemokines (CCL2, CCL3, CCL5), PDGF-BB, interleukins IL-6, IL-17, and sCD40L using Luminex™ xMAP® technology. After adjusting for age and medication use, the urine levels of analytes were correlated with the scales of obesity, prostate inflammation grade, extent, and markers of lymphocytic infiltration (CD3 and CD20) using linear regression. RESULTS: sIL-1RA levels were significantly raised with higher BMI, waist circumference and waist-hip ratio in BPH patients after correction for multiple testing (P = 0.02). Men with greater overall extent of inflammatory infiltrates and maximal CD3 infiltration were marginally associated with CXCL-10 (P = 0.054) and CCL5 (P = 0.054), respectively. CCL3 in 15 patients with moderate to severe grade inflammation was marginally associated with maximal CD20 infiltration (P = 0.09), whereas CCL3 was undetectable in men with mild prostate tissue inflammation. There was marginal association of sCD40L with AUA-SI scores (P = 0.07). CONCLUSIONS: Strong association of sIL-1RA in urine with greater body size supports it as a major molecular correlate of obesity in the urine of BPH patients. Increased urine levels of CXCL-10, CCL5, and CCL3 were marginally associated with the scores for prostate tissue inflammation and lymphocytic infiltration. Overall, elevated urinary chemokines support that BPH is a metabolic disorder and suggest a molecular link between BPH/LUTS and prostatic inflammation.

Phytoestrogen Concentrations in Human Urine as Biomarkers for Dietary Phytoestrogen Intake in Mexican Women.

There has been substantial interest in phytoestrogens, because of their potential effect in reducing cancer and heart disease risk. Measuring concentrations of phytoestrogens in urine is an alternative method for conducting epidemiological studies. Our objective was to evaluate the urinary excretion of phytoestrogens as biomarkers for dietary phytoestrogen intake in Mexican women. Participants were 100 healthy women from 25 to 80 years of age. A food frequency questionnaire (FFQ) and a 24 h recall were used to estimate habitual and recent intakes of isoflavones, lignans, flavonols, coumestrol, resveratrol, naringenin, and luteolin. Urinary concentrations were measured by liquid chromatography (HPLC) coupled to mass spectrometry (MS) using the electrospray ionization interface (ESI) and diode array detector (DAD) (HPLC-DAD-ESI-MS). Spearman correlation coefficients were used to evaluate associations between dietary intake and urine concentrations. The habitual consumption (FFQ) of total phytoestrogens was 37.56 mg/day. In urine, the higher compounds were naringenin (60.1 µg/L) and enterolactone (41.7 µg/L). Recent intakes (24 h recall) of isoflavones (r = 0.460, p < 0.001), lignans (r = 0.550, p < 0.0001), flavonoids (r = 0.240, p < 0.05), and total phytoestrogens (r = 0.410, p < 0.001) were correlated to their urinary levels. Total phytoestrogen intakes estimated by the FFQ showed higher correlations to urinary levels (r = 0.730, p < 0.0001). Urinary phytoestrogens may be useful as biomarkers of phytoestrogen intake, and as a tool for evaluating the relationship of intake and disease risk in Mexican women.

Influence of Ingesting a Flavonoid-Rich Supplement on the Metabolome and Concentration of Urine Phenolics in Overweight/Obese Women.

This study evaluated the effect of ingesting a flavonoid-rich supplement (329 mg/d) on total urine phenolics and shifts in plasma metabolites in overweight/obese female adults using untargeted metabolomics procedures. Participants (N = 103, 18-65 y, BMI ≥ 25 kg/m2) were randomized to flavonoid (F) or placebo (P) groups for 12 weeks with blood and 24 h urine samples collected prestudy and after 4 and 12 weeks in a parallel design. Supplements were prepared as chewable tablets and included vitamin C, wild bilberry fruit extract, green tea leaf extract, quercetin, caffeine, and omega 3 fatty acids. At 4 weeks, urine total phenolics increased 24% in F versus P with similar changes at 12 weeks (interaction effect, P = 0.041). Groups did not differ in markers of inflammation (IL-6, MCP-1, CRP) or oxidative stress (oxLDL, FRAP). Metabolomics data indicated shifts in 63 biochemicals in F versus P with 70% from the lipid and xenobiotics superpathways. The largest fold changes in F were measured for three gut-derived phenolics including 3-methoxycatechol sulfate, 3-(3-hydroxyphenyl)propanoic acid sulfate, and 1,2,3-benzenetriol sulfate (interaction effects, p ≤ 0.050). This randomized clinical trial of overweight/obese women showed that 12 weeks ingestion of a mixed flavonoid nutrient supplement was associated with a corresponding increase in urine total phenolics and gut-derived phenolic metabolites.