The role of caloric intake in the association of high salt intake with high blood pressure.

Since current recommendations call for a substantial reduction in overall sodium consumption, we tested whether or not these recommendations are implemented in common large subpopulations such as those with abnormal weight or hypertension in the current high sodium, high-calorie nutritional environment. In a national representative cross-sectional survey of the community-dwelling subjects aged 25-65 years conducted in Israel between 2015 and 2017, 582 randomly selected subjects completed health and dietary questionnaires, underwent blood pressure and anthropometric measurements and collected 24-h urine specimens, to assess dietary sodium intake. Overall mean 24-h sodium excretion was 3834 mg, more than double the recommended upper intake for adults < 1500 mg/day. Sodium excretion was directly related to caloric intake and blood pressure and linked to the presence of hypertension and overweight/obesity. The highest sodium excretion was seen in overweight/obese hypertensive subjects. This recent national survey shows a high consumption of sodium in the Israeli population and a dose-response association between caloric intake and urinary sodium excretion, independent of BMI and hypertension. Nevertheless, overweight/obese subjects with hypertension consume (excrete) more sodium than other BMI/ blood pressure-related phenotypes and may thus comprise a target subpopulation for future efforts to reduce sodium intake.

Reduction of Cardio-Metabolic Risk and Body Weight through a Multiphasic Very-Low Calorie Ketogenic Diet Program in Women with Overweight/Obesity: A Study in a Real-World Setting.

BACKGROUND: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. METHODS: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27-60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m2; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. RESULTS: The VLCKD program resulted in a significant decrease of body weight and BMI (-14.6%) and waist circumference (-12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (-3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. CONCLUSIONS: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.

Iodine Nutritional Status and Related Factors among Chinese School-Age Children in Three Different Areas: A Cross-Sectional Study.

We evaluated the iodine nutritional status and related factors among school-age children based on the 2016 National Nutrition and Health Surveillance of Children and Lactating Women; 3808 children from Hebei, Guangxi, and Zhejiang province were included in the study. Urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), body mass index (BMI), vitamin A (VA), and vitamin D (VD) were measured. The abnormal rate of UIC and TSH were assessed. Relationships between UIC/TSH and the possible factors were analyzed. The overall median UIC was 185.14 µg/L, and the median UIC of children aged 8-10 was 164.60 µg/L. Prevalence of iodine deficiency and excess was 13.84% and 14.36%, respectively, and 12.87% of children showed TSH excess. UIC, as well as the abnormal rates of iodine deficiency (ID) and TSH, were significantly different among the three provinces. The median UICs and excess rates increased with age, reaching 211.45 µg/L and 21.35% at age of 14~, while TSH showed the opposite trend. Overweight children tended to have lower UIC and higher TSH. Higher UIC and TSH were found in VA sufficient group (p < 0.01). Further, the VD deficient group had a higher TSH compared to the sufficient group (p < 0.01). Moreover, UI and TSH distribution was obviously different among different vitamin A/D status (p < 0.05). Although the median UIC of school-age children was optimal, there were pockets of inadequate and excessive UI in the three provinces. Compared to the national IDD monitoring results in 2014, the iodine nutritional status of children was greatly improved. Considerations of region, age, BMI, VA, or VD are needed in the future iodine evaluation and surveillance.

Beverages Based on Second Quality Citrus Fruits and Maqui Berry, a Source of Bioactive (Poly)phenols: Sorting Out Urine Metabolites upon a Longitudinal Study.

The intake of sugar-sweetened beverages has been associated with an augmented prevalence of metabolic diseases, namely, obesity, type II diabetes, and metabolic syndrome. On the other hand, nowadays, it is broadly accepted that foods and beverages rich in (poly)phenols could contribute to reducing the incidence of these pathologies. In this sense, the objective of the work was to revalue second quality citrus fruits for the development of new beverages, rich in anthocyanins and flavanones (maqui berry and second qualities citrus-based), and evaluate the influence of alternative sweeteners (sucralose, sucrose, or stevia), regarding the bioaccessibility and bioavailability of these bioactive compounds in the frame of a chronic (longitudinal) intervention. To fulfill this objective, a longitudinal study of the urinary excretion of anthocyanins and flavanones, after 2-months of ingestion of the developed maqui-citrus beverage, by 138 volunteers (n = 46 per beverage) and the analysis of the resulting phenolic metabolites by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-ESI-QqQ-MS/MS) was carried out. As major results, the bioavailable metabolites of caffeic acid (CA), catechol (CAT), 3,4-di-hydroxyphenylacetic acid (DHPAA), eriodictyol (E), homoeriodictyol (HE), hippuric acid (HA), naringenin (N), trans-ferulic acid (TFA), 2,4,6-tri-hydroxybenzaldehyde (THBA), trans-isoferulic acid (TIFA), and vanillic acid (VA) were detected. Accordingly, significantly different bioavailability was dependent on the sweetener used, allowing proposing stevia and, to a lower extent, sucralose, as valuable alternatives to sucrose.

Angiotensin-(3-4) normalizes blood pressure, decreases Na+ and energy intake, but preserves urinary Na+ excretion in overweight hypertensive rats.

Hypertension, one of the most common and severe comorbidities of obesity and overweight, is a worldwide epidemic affecting over 30% of the population. We induced overweight in young male rats (aged 58 days) by exposure to a hypercaloric high lipid (HL) diet in which 70% of the calories originated from fat. The HL diet also contained 33 or 57% higher Na+ than the control (CTR) diet. Over the following weeks the HL rats gradually became overweight (490 ± 12 g vs 427 ± 7 g in the CTR group after 15 weeks) with high visceral fat. They developed elevated systolic blood pressure (SBP) (141 ± 1.9 mmHg), which was fully restored to CTR values (128 ± 1.1 mmHg) by oral administration of Ang-(3-4) (Val-Tyr), the shortest renin-angiotensin-derived peptide. The overweight rats had lower plasma Na+ concentration that augmented to CTR values by Ang-(3-4) treatment. Na+ ingestion was depressed by 40% as result of the Ang-(3-4) treatment, whereas the urinary excretion of Na+ (UNaV) remained unmodified. The preservation of UNaV after Ang-(3-4) treatment - despite the sharp decrease in the dietary Na+ intake - can be ascribed to the normalization of renal type 1 angiotensin II receptors and Na+-transporting ATPases, both up-regulated in overweight rats. These renal effects complete a counterregulatory action on elevated renin-angiotensin activity that allows the high SBP to be normalized and body Na+ homeostasis to be restored concomitantly in overweight rats.

Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults.

Obesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R2 = 0.1384, P = 0.01) and diastolic BP (R2 = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R2 = 0.1232, P = 0.02) and partially correlated to urine protein (R2 = 0.047, P = 0.12) and FBG (R2 = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.

Orthostatic proteinuria: an overestimated phenomenon?

BACKGROUND: Although orthostatic proteinuria (OP) is the most common cause of childhood proteinuria, excluding transient proteinuria, data regarding prevalence and long-term prognosis are limited. We aimed to determine prevalence of OP in healthy schoolchildren evaluating relationships with age, gender and body mass index, and determine follow-up. METHODS: A total of 1701 healthy children aged 6-15 years were selected using a population-based, stratified, cluster-sampling method; and random urine samples were taken. For proteinuria ≥ 1+ in first urine samples, second and third random samples were taken at least 2 weeks apart to exclude transient proteinuria. For continuing proteinuria after third samples, first morning urine samples were collected. Cases where proteinuria was not detected in first morning urine samples were diagnosed as OP. RESULTS: Sixty-four of 1701 children (3.7%) had proteinuria on first random urine samples. After second and third urine samples, proteinuria persisted in only 16 (0.94%). OP was detected in 11 (0.65%). Prevalence of OP tended to decrease with increasing BMI, though not statistically significant. All 7 cases with OP who were re-evaluated later, had no proteinuria 3 years after diagnosis. CONCLUSIONS: Prevalence of OP in our study was lower than the literature. At least three random urine samples should be taken to exclude transient proteinuria in an asymptomatic child/adolescent before making a diagnosis of OP using first morning urine samples. OP is a benign condition and resolves spontaneously in most cases. Underweight children had a tendency for OP compared with overweight and obese children; however, further studies with larger number of patients are needed.

Urinary Metabolomic Profiling Analysis and Evaluation of the Effect of Ecklonia cava Extract Intake.

Metabolomics is a powerful tool for the investigation of interactions between diet, nutrients, and human metabolism. Ecklonia cava is an edible brown alga that is abundantly found in Korea and Japan and contains unique polyphenols referred to as phlorotannins. However, there are few metabolomics studies related to the effects of polyphenols in humans. In this study, we performed a mass spectrometry-based metabolomics analysis of urine samples from participants with a body mass index (BMI) higher than 25 kg/m2 and lower than 30 kg/m2 to investigate the effects of the intake of seapolynol isolated from E. cava. Metabolomic profiling showed that the levels of riboflavin, urocanic acid, 5-hydroxy-6-methoxyindole glucuronide, and guanidino valeric acid were significantly increased in the seapolynol intake group compared with the placebo group. A correlation analysis was performed to identify the association between the metabolites' levels and clinical characteristics related to body fat. Among the metabolites whose concentrations changed in the seapolynol intake group, riboflavin was associated with BMI, body weight, fat mass, and percent body fat. These findings suggest that the decreased body fat induced by the intake of seapolynol is related to an increase in the antioxidant effect of riboflavin.

Increased Aortic Characteristic Impedance Explains Relations Between Urinary Na+/K+ and Pulse or Systolic Blood Pressure.

Alterations in sodium (Na+) relative to potassium (K+) intake increase systolic blood pressure, effects in-part attributed to enhanced pulsatile loads (pulse pressure) beyond steady-state pressures (mean arterial pressure). Whether this effect is through reversible changes (increases in blood volume and hence aortic flow [Q] or wave reflection [Pb]), or potentially irreversible structural changes in the proximal aorta, is unknown. In 581 black South Africans, we determined 24-hour urinary Na+ and K+ excretion and aortic function from central aortic pressure (radial pulse wave analysis [SphygmoCor software]), velocity, and diameter measurements. Proximal aortic function was assessed from characteristic impedance (Zc). Beyond mean arterial pressure and additional confounders, urinary Na+/K+ was independently associated with Zc (P<0.005) but not peak aortic Q (P=0.30) or alternative aspects of Q or ejection volume. Although age was strongly associated with proximal aortic diameter, no independent relations between urinary Na+/K+ and aortic diameter were noted (P=0.17). Relations between urinary Na+/K+ and Zc translated into independent relations with early systolic compression wave pressures (QxZc [PQxZc]) and aortic forward wave pressures but not Pb. Moreover, neither reflected wave magnitude (P=0.92) nor aortic pulse wave velocity were independently associated with urinary Na+/K+. In product of coefficient mediation analysis, the independent relations between urinary Na+/K+ and peak aortic or brachial pulse pressure or systolic blood pressure were accounted for by Zc and PQxZc. In conclusion, abnormalities in Na+/K+ intake determine pulse pressure or systolic blood pressure beyond mean arterial pressure mainly through potentially irreversible impacts on proximal aortic impedance rather than readily modifiable increases in aortic flow (blood volume) or wave reflection.

Association of Adherence to The Mediterranean Diet with Urinary Factors Favoring Renal Lithiasis: Cross-Sectional Study of Overweight Individuals with Metabolic Syndrome.

Our purpose was to study the relationship of adherence to the Mediterranean diet (MedDiet) with urinary factors that favor the formation of renal calcium and uric acid stones in overweight and obese participants who had metabolic syndrome. This cross-sectional study examined 267 participants. A well-known MedDiet score (range 0-9) was calculated for each patient, and patients were then categorized has having low (≤3), medium (4-5), or high (≥6) adherence to the MedDiet. Baseline characteristics and urinary parameters were also analyzed. High calcium salt urinary crystallization risk (CaUCR) and high uric acid urinary crystallization risk (UrUCR) were calculated from urinary parameters using pre-defined criteria. More than half of patients with MedDiet scores ≤3 had high UrUCR (55.4%) and high CaUCR (53.8%). In contrast, fewer patients with high adherence (≥6) to the MedDiet had high UrUCR (41.2%) and high CaUCR (29.4%). Relative to those with low adherence, individuals with high adherence had a prevalence ratio (PR) of 0.77 for a high UrUCR (95% CI: 0.46-1.12; p for trend: 0.069) and a PR of 0.51 for a high CaUCR (95% CI: 0.26-0.87; p for trend: 0.012) after adjusting for age, sex, body mass index, type 2 diabetes, and total energy intake. Our findings indicate that greater adherence to the MedDiet was associated with a reduced CaUCR and a reduced UrUCR. This suggests that adequate dietary management using the MedDiet patterns may prevent or reduce the incidence and recurrence of calcium salt and uric acid renal stones.

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults.

Nicotinamide riboside (NR) is a newly discovered nicotinamide adenine dinucleotide (NAD+) precursor vitamin. A crystal form of NR chloride termed NIAGEN is generally recognized as safe (GRAS) for use in foods and the subject of two New Dietary Ingredient Notifications for use in dietary supplements. To evaluate the kinetics and dose-dependency of NR oral availability and safety in overweight, but otherwise healthy men and women, an 8-week randomized, double-blind, placebo-controlled clinical trial was conducted. Consumption of 100, 300 and 1000 mg NR dose-dependently and significantly increased whole blood NAD+ (i.e., 22%, 51% and 142%) and other NAD+ metabolites within 2 weeks. The increases were maintained throughout the remainder of the study. There were no reports of flushing and no significant differences in adverse events between the NR and placebo-treated groups or between groups at different NR doses. NR also did not elevate low density lipoprotein cholesterol or dysregulate 1-carbon metabolism. Together these data support the development of a tolerable upper intake limit for NR based on human data.

Asymmetric and Symmetric Protein Arginine Dimethylation: Concept and Postprandial Effects of High-Fat Protein Meals in Healthy Overweight Men.

Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) are risk factors for the cardiovascular and renal systems. There is a paucity of data in humans regarding variations of protein L-arginine (Arg) methylation leading to ADMA and SDMA. In this study, we introduced and used Arg dimethylation indices based on the creatinine-corrected urinary excretion of SDMA and ADMA, and its major metabolite dimethylamine (DMA). The main objective of the present study was to assess whether, and to which extent, a high-fat protein meal (HFM), a classical allostatic load eliciting various adverse effects, may contribute to Arg dimethylation in proteins in humans. Reliable gas chromatography-mass spectrometry methods were used to measure the concentration of ADMA, DMA, SDMA, and creatinine in spot urine samples collected before (0 h), and after (2, 4, 6 h) three HFM sessions in 10 healthy overweight individuals. At baseline, urinary ADMA, DMA, and SDMA excretion correlated positively with circulating TNF-α and IL-6. Arg dimethylation indices did not change postprandially. Our study shows that three HFMs do not contribute to Arg dimethylation in proteins. The proposed indices should be useful to determine extent and status of the whole-body Arg dimethylation in proteins in humans under various conditions.

Associations between urinary organophosphate ester metabolites and measures of adiposity among U.S. children and adults: NHANES 2013-2014.

BACKGROUND: Organophosphate esters (OPEs) are synthetic chemicals found in many consumer products, including furniture, electronics, processed foods, and building materials. Emerging in vitro and in vivo studies suggest that OPEs are metabolism disrupting compounds; however, epidemiologic studies investigating their associations with adiposity markers are sparse. OBJECTIVE: We examined cross-sectional associations between OPE biomarkers and adiposity measures among U.S. children and adults participating in the National Health and Nutrition Examination Survey (NHANES: 2013-2014). METHODS: Concentrations of five OPE metabolites were quantified in urine: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), and bis(1-chloro-2-propyl) phosphate (BCPP). We conducted covariate-adjusted logistic and linear regressions to examine associations between log2-transformed and dichotomized OPE metabolite concentrations and obesity, body mass index (BMI), and waist circumference (WC), separately among 784 children (6-19 years) and 1672 adults (≥20 years). We also assessed heterogeneity of associations by sex. RESULTS: DBUP concentrations were inversely associated with the prevalence odds of being obese vs. normal weight in children (adjusted Prevalence Odds Ratio, aPOR: 0.82, 95% Confidence Interval, 95% CI: 0.70, 0.95) and adults (aPOR: 0.83, 95% CI: 0.72, 0.96). DBUP was also significantly associated with lower BMI z-scores (ß:-0.08, 95% CI:-0.17, 0.01) and WC (ß:-0.71, 95% CI: -1.49, 0.07) in children. BCEP concentrations were associated with increased prevalence odds of being overweight vs. normal weight (aPOR: 1.15, 95% CI: 1.01, 1.32) among children; similar, albeit not statistically significant, relationships were observed with other child adiposity outcomes. Among adults, detectable BCPP concentrations were associated with increased prevalence odds of being obese vs. normal weight (aPOR: 1.70, 95% CI: 1.21, 2.38) and having a high vs. normal WC (aPOR: 1.51, 95% CI: 1.11, 2.07) as well as higher BMI (ß: 1.31, 95% CI: 0.30, 2.33). Other OPE metabolites were not consistently associated with adiposity measures among adults. Although associations of BCPP exposure with adiposity outcomes were generally inverse among boys, but not girls, we did not observe consistent evidence of sexually-dimorphic associations for other OPE metabolites. CONCLUSIONS: Exposure to select OPEs may be differentially associated with body size among children and adults. Given the cross-sectional design of the present study, future prospective studies are needed to confirm these findings.

Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial.

PURPOSE: We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. METHODS: 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m2) with abdominal adiposity (waist: hip > 0.8 for women and > 0.9 for men; waist: height ≥ 0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. RESULTS: Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P < 0.05). Interferon-γ was elevated (P < 0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P < 0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P < 0.05). CONCLUSIONS: An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Association of blood pressure with estimates of 24-h urinary sodium and potassium excretion from repeated single-spot urine samples.

While the association between 24-h urinary sodium and potassium excretion with blood pressure is well established, the relationships of these ions to spot urine measurements are unclear. Our purpose is to assess the association between blood pressure and the estimated 24-h sodium and potassium excretion from repeated single-spot urine samples. Spot urine and blood pressure were collected annually during a 5-year period from 4360 Japanese workers with ages ranging from 19 to 55 years. Estimates of 24-h sodium and potassium excretion were based on Tanaka's formula. Overall, a single standard deviation increase in the estimated sodium excretion (36.5 mmol/day) was associated with a 1.3 mmHg higher systolic blood pressure and a 0.8 mmHg higher diastolic blood pressure (P < 0.001). A single standard deviation increase in estimated potassium excretion (8.9 mmol/day) was associated with a 1.1 mmHg lower systolic blood pressure and a 0.7 mmHg lower diastolic blood pressure (P < 0.001). As a combined measure of the excretion of both electrolytes, the estimated 24-h sodium-to-potassium ratio was positively associated with both blood pressures (P < 0.001). Associations of blood pressure with sodium and the sodium-to-potassium ratio increased with age and were stronger in men compared to women. Associations with potassium and the sodium-to-potassium ratio were stronger in individuals who were overweight. The findings provide evidence for an association between blood pressure and the estimated 24-h sodium and potassium excretion from repeated single-spot urine samples. As convenient measures of dietary intake for each electrolyte, repeated spot urine samples may be useful for assessing hypertension risk, especially in men, older individuals, and overweight individuals.

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.

Untargeted metabolomics approach (UPLC-Q-TOF-MS) explores the biomarkers of serum and urine in overweight/obese young men.

BACKGROUND AND OBJECTIVES: Obesity is linked to metabolic diseases characterized by insulin resistance, such as diabetes and cardiovascular disease. In this study, we investigated the metabolic disorders of uncomplicated obesity to identify early alterations in biological systems. METHODS AND STUDY DESIGN: Metabolic differences between overweight/obese (n=36) and normal-weight (n=35) young Chinese men without known metabolic disorders were assessed. Metabolic profiling of the serum and urine was performed using ultra-performance liquidchromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Partial least squares discriminant analysis (PLS-DA) was undertaken to reveal and classify the differences between the two groups. RESULTS: Compared to normal-weight men, obese men had higher levels of the serum metabolites phenylalanine, Phe-Phe, and L-tryptophan, whereas those of p-cresol sulfate and p-cresol were less in obesity. Urinary metabolites phenylacetamide, L-glutamine, phenylacetylglutamine, indoxyl sulfate, p-cresol, and p-cresol sulfate were greater in obese men. CONCLUSIONS: These findings indicate that disorders involving aromatic amino acids and the tricarboxylic acid cycle (TCA) have microbiomic involvement in the uncomplicated phase of obesity.

Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in calcium stone formers.

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.

The effect of casein, hydrolyzed casein, and whey proteins on urinary and postprandial plasma metabolites in overweight and moderately obese human subjects.

BACKGROUND: Casein and whey proteins differ in amino acid composition and absorption rate; however, the absorption rate of casein can be increased to mimic that of whey proteins by exogenous hydrolysis. In view of these compositional differences, we studied the metabolic responses to intake of casein, hydrolyzed casein, and whey proteins in overweight and moderately obese men and women by investigating select urinary and blood plasma metabolites. RESULTS: A total of 21 urinary and 23 plasma metabolites were identified by nuclear magnetic resonance spectroscopy. The postprandial plasma metabolites revealed a significant diet-time interaction for isoleucine (P = 0.001) and tyrosine (P = 0.001). The level of isoleucine and tyrosine peaked 90 min postprandially with a 1.4-fold difference following intake of whey proteins compared with either casein or hydrolyzed casein. A 1.2-fold higher urinary level of lactate was observed after intake of whey proteins compared with intake of intact casein (P < 0.01). CONCLUSION: The plasma metabolites revealed different amino acid profiles reflecting the amino acid composition of casein and whey proteins. Furthermore, the results support that casein hydrolysates neither affect the postprandial amino acid absorption rate nor the amino acid level compared with that of intact casein. The urinary lactate increases following whey protein intake might indicate a higher metabolism of glucogenic amino acids. © 2018 Society of Chemical Industry.

Single and multiple dose evaluation of a novel MetAP2 inhibitor: Results of a randomized, double-blind, placebo-controlled clinical trial.

AIMS: Methionine aminopeptidase 2 (MetAP2) inhibition has been shown to result in significant weight loss and improved glucose control. This Phase 1 clinical trial assessed the safety and tolerability, pharmacokinetics and preliminary efficacy of a novel MetAP2 inhibitor, ZGN-1061. METHODS: This clinical trial included a single ascending dose (SAD) phase in healthy subjects (BMI, 23 to <30 kg/m2 ) and a multiple ascending dose (MAD) phase in otherwise healthy subjects (BMI, 27 to 40 kg/m2 ). SAD phase doses, administered subcutaneously (SC), were 0.2, 0.6, 1.2, 2.4, 3.6 and 4.8 mg and the MAD phase evaluated doses of 0.2, 0.6 and 1.8 mg twice weekly SC for 4 weeks. RESULTS: The SAD phase included 39 subjects (ZGN-1061, N = 28; placebo, N = 11); 90% were male and BMI was 26.4 kg/m2 . ZGN-1061 was well tolerated across all doses, with the most frequent adverse events being mild headache and procedural-related irritation. There were no severe or serious adverse events. All doses of ZGN-1061 were rapidly absorbed and cleared, resulting in short duration of exposure that is anticipated to minimize potential off-drug target risks. The MAD phase included 29 subjects (ZGN-1061, N = 22; placebo, N = 7); 76% were male and BMI was 33.5 kg/m2 . Safety observations were consistent with SAD findings. Efficacy measures in the MAD phase indicated trends for weight change (-1.5 kg total ZGN-1061 vs -0.2 kg placebo) and other biomarker changes. CONCLUSIONS: ZGN-1061 was well tolerated with no safety signals in all doses tested. In addition, the desired pharmacokinetic profile and preliminary efficacy observations with ZGN-1061 support evaluation in larger and longer clinical trials.