Rennan Feng

BMI is Strongly Associated With Hypertension, and Waist Circumference is Strongly Associated With Type 2 Diabetes and Dyslipidemia, in Northern Chinese Adults

Background Obesity is closely associated with chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), and dyslipidemia. We analyzed the optimal obesity index cut-off values for metabolic syndrome (MetS), and identified the obesity index that is more closely associated with these chronic diseases, in a population of northern Chinese. Methods We surveyed 8940 adults (age, 20–74 years) living in northern China for chronic diseases. Receiver operating characteristics (ROC) analysis, relative risk, and multivariate regression were used to develop an appropriate index and optimal cut-off values for MetS and obesity-related chronic diseases. Results Waist circumference (WC) and body mass index (BMI) were good markers for MetS, WC was a good marker for T2DM and dyslipidemia, and BMI was a good marker for hypertension. The optimal BMI cut-off value of MetS was 24 kg/m2, and the optimal WC cut-offs were 86 cm and 78 cm in men and women, respectively. Relative risk regression models showed that BMI was associated with hypertension, T2DM, and hypertriglyceridemia and a higher prevalence ratio (PR) for hypertension: 2.35 (95% CI, 2.18–2.50). WC was associated with T2DM, hypertension, and hypertriglyceridemia, with PRs of 2.05 (1.63–2.55) for T2DM and 2.47 (2.04–2.85) for hypertriglyceridemia. In multivariate regression models, the standardized regression coefficients (SRCs) of BMI were greater for SBP and DBP, and the SRC of WC was greater for fasting blood glucose, 2-hour postload blood glucose, triglyceride, and total cholesterol. Conclusions Our analysis of a population of northern Chinese indicates that the optimal cut-off values for MetS are WCs of 86 cm in men and 78 cm in women and a BMI of 24 kg/m2 in both sexes. BMI was strongly associated with hypertension, while WC was strongly associated with T2DM and dyslipidemia.

Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK.

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism.

The phytochemical, EGCG, extends lifespan by reducing liver and kidney function damage and improving age-associated inflammation and oxidative stress in healthy rats.

It is known that phytochemicals have many potential health benefits in humans. The aim of this study was to investigate the effects of long‐term consumption of the phytochemical, epigallocatechin gallate (EGCG), on body growth, disease protection, and lifespan in healthy rats. 68 male weaning Wistar rats were randomly divided into the control and EGCG groups. Variables influencing lifespan such as blood pressure, serum glucose and lipids, inflammation, and oxidative stress were dynamically determined from weaning to death. The median lifespan of controls was 92.5 weeks. EGCG increased median lifespan to 105.0 weeks and delayed death by approximately 8–12 weeks. Blood pressure and serum glucose and lipids significantly increased with age in both groups compared with the levels at 0 week. However, there were no differences in these variables between the two groups during the whole lifespan. Inflammation and oxidative stress significantly increased with age in both groups compared with 0 week and were significantly lower in serum and liver and kidney tissues in the EGCG group. Damage to liver and kidney function was significantly alleviated in the EGCG group. In addition, EGCG decreased the mRNA and protein expressions of transcription factor NF‐κB and increased the upstream protein expressions of silent mating type information regulation two homolog one (SIRT1) and forkhead box class O 3a (FOXO3a). In conclusion, EGCG extends lifespan in healthy rats by reducing liver and kidney damage and improving age‐associated inflammation and oxidative stress through the inhibition of NF‐κB signaling by activating the longevity factors FoxO3a and SIRT1.

Meta-analysis of TNF 308 G/A polymorphism and type 2 diabetes mellitus.

Background and Objectives Many investigations have focused the association between TNF 308 G/A polymorphism and risk for type 2 diabetes mellitus (T2DM). However, the sample sizes of most of the studies were small. The aim of this study is to evaluate the precise association between this variant and risk for T2DM in a large-scale meta-analysis. Methods All publications were searched on the association between TNF 308 G/A polymorphism and T2DM. The key words were as follows: diabetes, tumor necrosis factor and polymorphism/variant/genotype. This meta-analysis was assessed by Review manager 5.0. Results There were 18 studies identified. The odd ritos (ORs) and 95% confidence intervals (CI) for GA+AA versus GG genotype of TNF 308 G/A polymorphism were 1.03 (0.95–1.12), 1.03 (0.94–1.13) and 1.03 (0.78–1.36) in overall, Caucasian and Asian populations, respectively. The sensitivity analysis further strengthened the validity of this association. No publication bias or heterogeneity was observed in this study. Conclusion In summary, there was no significant association detected between the TNF 308 G/A polymorphism and risk for T2DM.

Cell adhesion molecules contribute to Alzheimer's disease: multiple pathway analyses of two genome-wide association studies

J. Neurochem. (2012) 120, 190–198.

PICALM Gene rs3851179 Polymorphism Contributes to Alzheimer’s Disease in an Asian Population

PICALM gene rs3851179 polymorphism was reported to an Alzheimer’s disease (AD) susceptibility locus in a Caucasian population. However, recent studies reported consistent and inconsistent results in an Asian population. Four studies indicated no association between rs3851179 and AD in a Chinese population and one study reported weak association in a Japanese population. We consider that the failure to replicate the significant association between rs3851179 and AD may be caused by at least two reasons. The first reason may be the genetic heterogeneity in AD among different populations, and the second may be the relatively small sample size compared with large-scale GWAS in Caucasian ancestry. In order to confirm this view, in this research, we first evaluated the genetic heterogeneity of rs3851179 polymorphism in Caucasian and Asian populations. We then investigated rs3851179 polymorphism in an Asian population by a pooled analysis method and a meta-analysis method. We did not observe significant genetic heterogeneity of rs3851179 in the Caucasian and Asian populations. Our results indicate that rs3851179 polymorphism is significantly associated with AD in the Asian population by both pooled analysis and meta-analysis methods. We believe that our findings will be very useful for future genetic studies in AD.

Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population

AIM To study the prevalence and clinical biochemical, blood cell and metabolic features of lean-non-alcoholic fatty liver disease (lean-NAFLD) and its association with other diseases. METHODS Demographic, biochemical and blood examinations were conducted in all the subjects in this study. We classified the subjects into four groups according to their weight and NAFLD status: lean-control, lean-NAFLD [body mass index (BMI) < 24 kg/m(2)], overweight-obese control and overweight-obese NAFLD. One-way analysis of variance (ANOVA) was used to compare the means of continuous variables (age, BMI, blood pressure, glucose, lipid, insulin, liver enzymes and blood cell counts) and the χ (2) test was used to compare the differences in frequency of categorical variables (sex, education, physical activity, smoking, alcohol consumption and prevalence of hypertension, hyperlipidemia, diabetes, metabolic syndrome central obesity and obesity). Both univariate and multivariate logistic regression models were adopted to calculate odds ratios (ORs) and predict hyperlipidemia, hypertension, diabetes and metabolic syndrome when we respectively set all controls, lean-control and overweight-obese-control as references. In multivariate logistic regression models, we adjusted potential confounding factors, including age, sex, smoking, alcohol consumption and physical activity. RESULTS The prevalence of NAFLD was very high in China. NAFLD patients were older, had a higher BMI, waist circumference, blood pressure, fasting blood glucose, insulin, blood lipid, liver enzymes and uric acid than the controls. Although lean-NAFLD patients had lower BMI and waist circumstance, they had significantly higher visceral adiposity index than overweight-obese controls. Lean-NAFLD patients had comparable triglyceride, cholesterin and low-density lipoprotein cholesterin to overweight-obese NAFLD patients. In blood cell examination, both lean and overweight-obese NAFLD was companied by higher white blood cell count, red blood cell count, hemoglobin and hematocrit value. All NAFLD patients were at risk of hyperlipidemia, hypertension, diabetes and metabolic syndrome (MetS). Lean-NAFLD was more strongly associated with diabetes (OR = 2.47, 95%CI: 1.14-5.35), hypertension (OR = 1.72, 95%CI: 1.00-2.96) and MetS (OR = 3.19, 95%CI: 1.17-4.05) than overweight-obese-NAFLD (only OR for MetS was meaningful: OR = 1.89, 95%CI: 1.29-2.77). NAFLD patients were more likely to have central obesity (OR = 1.97, 95%CI: 1.38-2.80), especially in lean groups (OR = 2.17, 95%CI: 1.17-4.05). CONCLUSION Lean-NAFLD has unique results in demographic, biochemical and blood examinations, and adds significant risk for diabetes, hypertension and MetS in lean individuals.

Increased levels of IL-23 and osteopontin in serum and cerebrospinal fluid of multiple sclerosis patients

Osteopontin (OPN) and interleukin-23 (IL-23) are pro-inflammatory cytokines proposed to play central roles to the development of multiple sclerosis (MS). The aim of this study was to evaluate levels of OPN, IL-23 and other inflammatory cytokines and investigate their relationships in serum and cerebrospinal fluid (CSF) in patients with MS. Fifty one MS patients and 48 patients with non-inflammatory neurological diseases (NIND) were recruited from clinic. The levels of OPN, IL-23, IL-17, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in serum and CSF were determined in each participant. Compared with NIND group, MS patients had significantly elevated levels of OPN, IL-23, IL-17 and TNF-alpha in CSF, and elevated levels of IL-23, IL-17 and TNF-alpha in serum (All P<0.001). In MS patients, OPN and IL-23 were positively correlated with IL-17 (r=0.302, P=0.019; r=0.417, P=0.001, respectively); and IL-23 was positively correlated with EDSS (r=0.329, P=0.019). Both OPN and IL-23 may play pivotal role in development of MS and might be specific markers and therapeutic targets for MS.

Dietary calcium but not elemental calcium from supplements is associated with body composition and obesity in Chinese women.

Objective We assessed whether dietary calcium intake or calcium supplements associated with body composition and obesity in a Chinese population. Methods A cross-sectional survey was performed in a population of 8940, aged 20 to 74 y. 8127 participants responded (90.9%). Height, weight, fat mass (FM), waist circumference (WC) and hip circumference were measured. Obesity definition: body mass index (BMI) ≥28 kg/m2 (overall obesity); WC ≥85 cm for men or ≥80 cm for women (abdominal obesity І) and waist hip ratio (WHR) ≥0.90 for men or ≥0.85 for women (abdominal obesity П). The data on dietary calcium and calcium supplements were collected using food-frequency questionnaire and self-report questionnaire. Multivariate linear and multivariable logistic regressions were used to examine the associations between dietary calcium intake or calcium supplements and body composition and obesity. Principal Findings The average dietary calcium intake of all subjects was 430 mg/d. After adjusting for potential confounding factors, among women only, negative associations were observed between habitual dietary calcium intake and four measures of body composition (β, −0.086, P<0.001 for BMI; β, −0.072, P<0.001 for WC; β, −0.044, P<0.05 for WHR; and β, −0.058, P<0.01 for FM, respectively) and both measures of abdominal obesity (Odds Ratio [OR] = 0.86, 95% Confidence Interval [CI], 0.80–0.93; P<0.001, for abdominal obesity I; OR = 0.92, 95% CI, 0.86–0.99; P = 0.026, for abdominal obesity II). These associations were not observed among men (P>0.05). Similarly, among both men and women, we did not observe significant associations between calcium supplements and any measures of body composition or abdominal obesity (P>0.05). Conclusions Dietary calcium from food rather than elemental calcium from calcium supplements has beneficial effects on the maintenance of body composition and preventing abdominal obesity in Chinese women.

Metabolic profiling of urine in young obese men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC/Q-TOF MS)

Obesity is currently epidemic in many countries worldwide. In the young adult, obesity often accompanies hyperlipemia, which is strongly related to the occurrence and development of obesity-related chronic diseases such as diabetes mellitus, hypertension and cardiovascular disease. This study investigated the differences in metabolomic profiling between obese (with hyperlipemia, n=30) and normal-weight (n=30) young men. Anthropometric parameters and conventional metabolites were measured. There were no significant differences between obese and normal-weight young men in age, height and fasting plasma glucose level. Obese young men showed increased weight, body mass index, fat mass, systolic blood pressure, and triglyeride, total cholesterol and insulin levels, and lower levels of testosterone. The endogenous metabolite profile of urine was investigated by UPLC/Q-TOF MS (ultra performance liquid chromatography and Q-TOF mass spectrometry) with electrospray ionization (ESI). Partial least squares (PLS) enabled clusters to be visualized. Eight urine principal metabolites contributing to the clusters were identified; these included increased L-prolyl-L-proline, leucyl-phenylalanine, and decanoylcarnitine in positive ESI mode (m/z 213.1267, 279.1715 and 316.2459, respectively) and N-acetylornithine, 17-hydroxypregnenolone sulfate, 11β-hydroxyprogesterone, 5a-dihydrotestosterone sulfate and glucosylgalactosyl hydroxylysine in negative ESI mode (m/z 173.0931, 411.1883, 331.185, 369.1751 and 485.1875, respectively). These metabolite changes in obese men suggested early changes of metabolism in young-male obesity with hyperlipemia. The study may further aid the clinical prevention and treatment of obesity and related chronic disease.