Adjusted odds ratios (ORs) with 95% confidence interval (CI) of metabolic syndrome and its components according to age at first delivery.

<p>Adjusted for age, current smoking, regular exercise, alcohol intake, number of pregnancies, age at menarche, hormone replacement therapy and daily total energy intake.</p><p>Adjusted odds ratios (ORs) with 95% confidence interval (CI) of metabolic syndrome and its components according to age at first delivery.</p

Adjusted odds ratios with 95% confidence interval for the presence of low bone mineral density for each standard deviation (SD) increase in serum creatinine.

<p>*Data were adjusted for age, current smoking status, regular exercise, daily calcium intake (mg/d), HOMA-IR, vitamin D, body fat (%) and estrogen replacement therapy (in women).</p

Multivariate odds ratio and 95% confidence interval for low bone mineral density^a according to serum creatinine.

<p>^aLow bone mineral density: T-score ≤ –1.0</p><p>^bData are presented using a Chi-square test</p><p>Model 1: adjusted for age; Model 2: Model 1+ further adjusted for regular exercise, alcohol intake, current smoking status, 25(OH)D and estrogen replacement therapy (women); Model 3: Model 2+ further adjusted for HOMA-IR, daily calcium intake and body fat (%).</p><p>Multivariate odds ratio and 95% confidence interval for low bone mineral density<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0133062#t003fn001" target="_blank">^a</a> according to serum creatinine.</p

Lower Serum Creatinine Is Associated with Low Bone Mineral Density in Subjects without Overt Nephropathy

<div><p>Background</p><p>Low skeletal muscle mass is associated with deterioration of bone mineral density. Because serum creatinine can serve as a marker of muscle mass, we evaluated the relationship between serum creatinine and bone mineral density in an older population with normal renal function.</p><p>Methods</p><p>Data from a total of 8,648 participants (4,573 men and 4,075 postmenopausal women) aged 45–95 years with an estimated glomerular filtration rate >60 ml/min/1.73 m2 were analyzed from the Fourth Korea National Health and Nutrition Examination Survey (2008–2010). Bone mineral density (BMD) and appendicular muscle mass (ASM) were measured using dual-energy X-ray absorptiometry. Receiver operating characteristic curve analysis revealed that the cut points of serum creatinine for sarcopenia were below 0.88 mg/dl in men and 0.75 mg/dl in women. Subjects were divided into two groups: low creatinine and upper normal creatinine according to the cut point value of serum creatinine for sarcopenia.</p><p>Results</p><p>In partial correlation analysis adjusted for age, serum creatinine was positively associated with both BMD and ASM. Subjects with low serum creatinine were at a higher risk for low BMD (T-score ≤ –1.0) at the femur neck, total hip and lumbar spine in men, and at the total hip and lumbar spine in women after adjustment for confounding factors. Each standard deviation increase in serum creatinine was significantly associated with reduction in the likelihood of low BMD at the total hip and lumbar spine in both sexes (men: odds ratio (OR) = 0.84 [95% CI = 0.74−0.96] at the total hip, OR = 0.8 [95% CI = 0.68−0.96] at the lumbar spine; women: OR = 0.83 [95% CI = 0.73–0.95] at the total hip, OR=0.81 [95% CI = 0.67–0.99] at the lumbar spine).</p><p>Conclusions</p><p>Serum creatinine reflected muscle mass, and low serum creatinine was independently associated with low bone mineral density in subjects with normal kidney function.</p></div

Characteristics of the study population according to the maternal age at first delivery.

<p>Data presented as age-adjusted mean ± standard error or n (%), except for age.</p><p>^a Non-adjusted values</p><p>BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; HbA1c: Hemoglobin A1c; HOMA-IR: homeostasis model assessment-insulin resistance; LDL: low-density lipoprotein; HDL: high-density lipoprotein; ASM: appendicular skeletal mass</p><p>^†: The difference between ≤ 20 and 21–25: p<0.05 after post hoc comparison (Bonferroni test for continuous variables)</p><p>^‡: The difference between ≤ 20 and ≥26: p<0.05 after post hoc comparison (Bonferroni test for continuous variables)</p><p>^#: The difference between 21–25 and ≥26: p<0.05 after post hoc comparison (Bonferroni test for continuous variables)</p><p>Characteristics of the study population according to the maternal age at first delivery.</p

Adjusted mean trunk fat mass (A), waist circumference (B) and body mass index (BMI) (C) in the different age at first delivery groups.

<p>Data are expressed as estimated marginal mean and standard error (*, P<0.05 by ANCOVA after controlling for adjusted for age, number of pregnancies, age at menarche, total energy intake, regular exercise and hormone replacement therapy with Bonferroni correction). Box and whisker plots of the trunk fat mass (D), waist circumference (E) and BMI (F) among different age at first delivery groups. Boxes show interquartile range with median indicated, and the whiskers indicate the minimum and maximum value (#, P<0.05 by ANOVA with Bonferroni correction).</p

α-Mangostin ameliorates hepatic steatosis and insulin resistance by inhibition C-C chemokine receptor 2

<div><p>Obesity induces various metabolic diseases such as dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. Fat expansion in adipose tissue induces adipose tissue dysfunction and inflammation, insulin resistance, and other metabolic syndromes. α-Mangostin (α-MG) has been previously studied for its anti-cancer, anti-inflammatory, and antioxidant activities. In this study, we investigated the effects of α-MG on adipose tissue inflammation and hepatic steatosis. We categorized study animals into four groups: regular diet control mice, RD mice treated with α-MG, high fat diet-induced obese mice, and HFD mice treated with α-MG. α-MG treatment significantly reduced not only the body, liver, and fat weights, but also plasma glucose, insulin, and triglyceride levels in HFD mice. Additionally, adiponectin levels of α-MG-treated mice were significantly higher than those of control HFD mice. Immunohistochemistry of liver and adipose tissue showed that CD11c expression was reduced in α-MG fed obese mice. α-MG treatment of HFD mice down-regulated the adipose-associated inflammatory cytokines and CCR2 in both liver and adipose tissue. Moreover, glucose tolerance and insulin sensitivity were significantly improved in α-MG fed obese mice. α-Mangostin ameliorates adipose inflammation and hepatic steatosis in HFD-induced obese mice.</p></div

SH inhibition of NRK52E cell glucotoxicity depends on the AMPK-SIRT1-PGC1alpha axis and inflammatory signals.

<p>NRK52E cells were stimulated by HG with or without SH and analyzed of phosphorylated AMPK, Sirt1, PGC1α and Cldn1 expressions (A and B). Andinflammatory molecules such as phosphorylated p38 and phosphorylated JNK changes were analyzed in HG with or without SH cultured NRK52E cells (C and D). LG, 5.5 mM D-glucose; HG, 30 mM D-glucose; SH, sarpogrelate hydrochloride. Values shown are mean ± SEM. ^*<i>p</i> < 0.05 vs. LG, ^†<i>p</i> < 0.05 vs. HG.</p

α-MG reduced inflammatory cell migration and cytokines.

<p>(A) Peritoneal macrophages and (B) Raw 264.7 (macrophage) cells were treated with CCL2 (10 ng/ml) or ATCM (adipose tissue-conditioned medium) in the presence and absence of CCR2 inhibitor (10 μM/ml) or α-MG (25 μM/ml) for 24h. The number of transmigrated peritoneal macrophages was measured using a migration assay in the presence and absence of α-MG. Original magnification is x200 (scale bar = 100 μm). (C) mRNA expression of pro-inflammatory cytokines (TNF-α, MCP-1, CCR2, and IL-6) and the anti-inflammatory cytokine IL-10 in Raw264.7 cells. mRNA levels were estimated using real-time PCR. *P < 0.05 compared to control. #P < 0.05 compared to CCL2 or ATCM treated.</p

Sarpogrelate hydrochloride ameliorates diabetic nephropathy associated with inhibition of macrophage activity and inflammatory reaction in <i>db/db</i> mice

<div><p>The aim of this study was to evaluate the effects of sarpogrelate hydrochloride (SH), a selective serotonin 2A receptor antagonist, on diabetic nephropathy in a type 2 diabetes mouse model. We treated <i>db/m</i> and <i>db/db</i> mice with SH (30 mg/kg/day) for 12 weeks. Rat renal proximal tubule cells (NRK-52E) and mouse macrophages (Raw 264.7) were stimulated by high glucose (30 mM glucose) or LPS (100 ng/ml) with or without SH (20 μM). We found that SH treatment increased serum adiponectin level and decreased urinary albumin, macrophage infiltration to glomeruli, and renal inflammatory and fibrosis signals, which were highly expressed in diabetic mice. Proximal tubule cells treated with high glucose (30 mM) also showed increased inflammatory and fibrosis signals. However, SH (20 μM) treatment reduced these changes. Moreover, SH treatment inhibited LPS-stimulated macrophage migration and activation. These findings suggest that SH ameliorates diabetic nephropathy not only by suppressing macrophage infiltration, but also by anti-inflammatory and anti-fibrotic effects.</p></div