Association between metabolically healthy central obesity in women and levels of soluble receptor for advanced glycation end products, soluble vascular adhesion protein-1, and the activity of semicarbazide-sensitive amine oxidase

Aim To determine the levels of circulating soluble receptor for advanced glycation end products (sRAGE), as a biomarker of risk of metabolic syndrome and cardiovascular disease development in centrally obese (CO) women considered metabolically healthy (COH) in comparison with those metabolically unhealthy (COU). Methods 47 lean healthy, 17 COH (presenting waist-toheight ratio ≥0.5 but not elevated blood pressure, atherogenic lipid profile, and insulin resistance), and 50 COU (CO presenting ≥2 risk factors) women aged 40-45 years were included. Anthropometric characteristics, blood chemistry and hematology data, adipokines, markers of inflammation, sRAGE, soluble vascular adhesion protein-1 (sVAP-1), and the activity of semicarbazide sensitive amine oxidase (SSAO) were determined. Results Central obesity associated with low sRAGE levels (lean healthy: 1503 ± 633 pg/mL; COH: 1103 ± 339 pg/mL, P < 0.05; COU: 1106 ± 367 ng/mL, P < 0.0.1), hyperleptinemia, and elevated markers of inflammation irrespective of the presence or absence of cardiometabolic risk factors. COU women presented high adiponectin levels. SVAP-1 concentrations and the activity of SSAO were similar in all 3 groups. Conclusion COH women present abnormalities in nonstandard markers of cardiometabolic risk (sRAGE, leptin, high sensitive C-reactive protein), supporting the view that there is no healthy pattern of obesity. The clinical impact of our findings for future prognosis of metabolically healthy obese subjects remains to be elucidated in longitudinal studies

Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats.

AIM: To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. METHODS: At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. RESULTS: MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. CONCLUSION: Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life

Influence Of Intensive Exercise On Renal Functions (Rf) And Advanced Glycation End-Products (Ages)

Under certain pathologic conditions AGEs formation can be increased beyond normal levels.The purpose of the study was to investigate essential RF and AGEs before, immediately after and 2 days after runs. Nine trained runners (43±9yr) during 9.5 km and 13 trained runners (48±11yr) during 16.3 km long-distance runs were investigated. Standard blood and urinary RF parameters were investi-gated in all runners using spectrophotometric methods by Roche analyzer Integra 800.Serum cystatin C was determined using immu-noturbidimetric method (PETIA Gentian). Plasma AGEs and malon-dialdehyde (MDA) were determined by spectrofluorimetric methods, Nε-carboxylmethyllysine using ELISA method and advanced oxidation protein products(AOPPs) using spectrophotometric method. Total proteinuria was 0.46±0.4 g/L after 9.5 km run and 0.35±0.3 g/L after 16.3 km run. Serum urea and creatinine significantly increased after both runs (creatinine in 28% after 9.5 km and in 41% after 16.3 km run). Estimated glomerular filtration rate (eGFR) MDRD and eGFR-PETIA significantly decreased after both runs (9.5 km: in 27.6% resp. 21.3% and 16.3 km: in 34,6% resp. 30.3%, p<0.01). Direct relationship between serum cystatin C and plasma AGEs after 16.3 km run was found (r=0.66, p=0,014). No significant changes in plasma AGEs (from 277±86—286±72 resp. from 283±64—292±90 AU), CML (from 619±78–665±131 resp. from 724±92—762±135 ng/mL) and AOPPs (from 151±58—106±21 resp. from 159±100–133±67 μmol/L) were found after both runs. Plasma MDA decreased after both runs. In conclusion, RF abnormalities in runners were caused by dehydration, protein catabolism, rhabdomyolysis and others. These RF changes were not present or parameters not significantly differed from initial values 2 days after both runs. Plasma AGEs and AOPPs in runners were in reference ranges, no significant changes during the both runs were observed

Plasma 25(OH)D₃ concentration according to absence or presence of cardiometabolic risk factors.

<p>Central obesity: waist-to-height ration >0.5 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref031" target="_blank">31</a>]; elevated blood pressure (BP): systolic BP ≥130 mm Hg and/or diastolic BP ≥85 mm Hg; increased atherogenic risk: AIP≥0.11 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref029" target="_blank">29</a>]; and insulin resistance: QUICKI<0.322 were considered as factors indicated increased cardiometabolic risk. 0: no risk factor presented (n = 162); 1–2: subjects with 1 or 2 risk factors (n = 162); 3–4: subjects presenting 3 or 4 risk factors (n = 87). Data are given as interquartile range (box), 5^th and 95^th percentile (whiskers). Statistical evaluation was performed on natural ln-transformed data. ANOVA: p<0.001, Scheffe’s post hoc test p indicated.</p

Functional and Partial Morphological Regression of Established Renal Injury in the Obese Zucker Rat by Blockade of the Renin-Angiotensin System

Background/Aims: In experimental nephropathies, inhibitors of the renin-angiotensin-system (RAS) halted the progression, or even induced a regression in renal injury. We studied the potential of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin receptor blocker candesartan to reverse the established renal injury in the obese Zucker rat (OZR). Methods: Forty 4-week-old OZRs were uninephrectomized and fed a high-protein diet. After 16 weeks, they were randomized into 4 groups (n = 10 each) with comparable proteinuria: (1) control group sacrificed immediately for baseline data, and groups gavaged daily for 8 weeks with (2) placebo, (3) perindopril (1 mg/kg/ day), or (4) candesartan (10 mg/kg/day). Results: Both drugs reduced systolic blood pressure (perindopril –16%, p ! 0.001; candesartan –10%, p ! 0.05), renal hypertrophy, and proteinuria (perindopril to 32%; candesartan to 37% of pretreatment values). Glomerulosclerosis was halted (perindopril p ! 0.001; candesartan p ! 0.05), and the numbers of glo- merular endothelial and podocyte cells were restored. Mesangiolysis was reversed by perindopril. Metabolic and oxidative parameters were either stabilized (perindopril), or improved (candesartan). Conclusion: In the OZR late inhibition of RAS halts the progression of glomerulosclerosis, reverses mesangiolysis and prevents the decline in glomerular endothelial cell and podocyte numbers. Tubulointerstitial fibrosis and vascular injury remain unchanged. Proteinuria shows marked regression

Decision tree.

<p>Std. Dev: standard deviation; BP: blood pressure; Adj.: adjusted; df: degree of freedom; EBP: elevated blood pressure (systolic BP ≥130 mm Hg and/or diastolic BP ≥85 mm Hg); NT: normotension; IRIS: insulin sensitivity (IS)/insulin resistance (IR); AIP: atherogenic index of plasma (AIP≥0.11 indicates increased atherogenic risk [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref029" target="_blank">29</a>])</p

Cohort characteristics: anthropometric data, blood pressure, standard blood chemistry variables and 25(OH)D₃ levels.

<p>Central obesity: waist-to-height ration >0.5 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref031" target="_blank">31</a>]; elevated BP: systolic BP (SBP)≥130 mm Hg and/or diastolic BP (DBP)≥85 mm Hg; increased atherogenic risk: AIP≥0.11 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref029" target="_blank">29</a>]; and insulin resistance: QUICKI<0.322 were considered as factors indicated increased cardiometabolic risk. 0: no risk factor presented (n = 162); 1–2: subjects with 1 or 2 risk factors (n = 162); 3–4: subjects presenting 3 or 4 risk factors (n = 87); F: females; M: males; BMI: body mass index; ICO: index of central obesity; SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure; PP: pulse pressure; FPG: fasting plasma glucose; FIns: fasting plasma insulin; QUICKI: quantitative insulin sensitivity check index; CHOL: total cholesterol; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol; VLDL-C: very low density lipoprotein cholesterol; TAG: triacylglycerols; AIP: atherogenic index of plasma; eGFR: estimated glomerular filtration rate; Vitamin D₃: plasma 25(OH)D₃; PTH: intact parathormone; chi: chi-square</p><p>*: p<0.05 vs. cardiometabolic risk factors free subjects</p><p>**: p<0.01 vs. cardiometabolic risk factors free subjects</p><p>***: p<0.001 vs. cardiometabolic risk factors free subjects</p><p>+: p<0.05 vs. subjects presenting 1 or 2 cardiometabolic risk factors</p><p>++: p<0.01 vs. subjects presenting 1 or 2 cardiometabolic risk factors</p><p>+++: p<0.001 vs. subjects presenting 1 or 2 cardiometabolic risk factors; <i>italics</i>: statistical evaluation performed on logarithmically transformed data</p><p>Cohort characteristics: anthropometric data, blood pressure, standard blood chemistry variables and 25(OH)D₃ levels.</p

Cohort characteristics: inflammatory and oxidative stress markers, adipokines and advanced glycation end products.

<p>Central obesity: waist-to-height ration >0.5 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref031" target="_blank">31</a>]; elevated BP: systolic BP (SBP)≥130 mm Hg and/or diastolic BP (DBP)≥85 mm Hg; increased atherogenic risk: AIP≥0.11 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref029" target="_blank">29</a>]; and insulin resistance: QUICKI<0.322 were considered as factors indicated increased cardiometabolic risk. 0: no risk factor presented (n = 162); 1–2: subjects with 1 or 2 risk factors (n = 162); 3–4: subjects presenting 3 or 4 risk factors (n = 87); hsCRP: high sensitive C-reactive protein; IL-6: interleukine-6; hsTNF-α: high sensitive tumor necrosis factor-α; CML: N^ε-(carboxymethyl)lysine; Alb: albumin; AGE-Fl: advanced glycation end products associated fluorescence of plasma; AU: arbitrary units; AOPP: advanced oxidation protein products; sRAGE: soluble receptor for advanced glycation end products</p><p>*: p<0.05 vs. cardiometabolic risk factors free subjects</p><p>**: p<0.01 vs. cardiometabolic risk factors free subjects</p><p>***: p<0.001 vs. cardiometabolic risk factors free subjects</p><p>+: p<0.05 vs. subjects presenting 1 or 2 cardiometabolic risk factors</p><p>++: p<0.01 vs. subjects presenting 1 or 2 cardiometabolic risk factors</p><p>+++: p<0.001 vs. subjects presenting 1 or 2 cardiometabolic risk factors; <i>italics</i>: statistical evaluation performed on logarithmically transformed data</p><p>Cohort characteristics: inflammatory and oxidative stress markers, adipokines and advanced glycation end products.</p

25(OH)D₃ status and plasma levels according to presence of cardiometabolic risk factors.

<p>Central obesity: waist-to-height ration >0.5 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref031" target="_blank">31</a>]; elevated BP: systolic BP (SBP)≥130 mm Hg and/or diastolic BP (DBP)≥85 mm Hg; increased atherogenic risk: AIP≥0.11 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref029" target="_blank">29</a>]; and insulin resistance: QUICKI<0.322 were considered as factors indicated increased cardiometabolic risk. 0: no risk factor presented (n = 162); 1–2: subjects with 1 or 2 risk factors (n = 162); 3–4: subjects presenting 3 or 4 risk factors (n = 87); chi: chi-square; otherwise ANOVA p indicated; <i>italics</i>: statistical evaluation performed on logarithmically transformed data</p><p>25(OH)D₃ status and plasma levels according to presence of cardiometabolic risk factors.</p