Yucun Niu

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.

Fasting Serum Lipid and Dehydroepiandrosterone Sulfate as Important Metabolites for Detecting Isolated Postchallenge Diabetes: Serum Metabolomics via Ultra-High-Performance LC-MS

BACKGROUND Isolated postchallenge diabetes (IPD), a subtype of type 2 diabetes mellitus (T2DM) defined as 2-h postprandial plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L) and fasting plasma glucose (FPG) <108 mg/dL (<6.0 mmol/L), is often overlooked during screening for diabetes on the basis of FPG concentrations. A key challenge is early identification of IPD by the use of fasting serum, which is critical for large-scale diabetes screening. METHODS We applied a nontargeted metabolomic approach using ultra-high-performance liquid chromatography-quadrupole TOF-mass spectrometry (UPLC-QTOF-MS) to analyze serum samples from 51 patients with IPD, 52 with newly diagnosed T2DM, and 49 healthy individuals. We processed metabolite profiles by multivariate analysis to identify potential metabolites, which were further confirmed by tandem MS (MS/MS). We also used GC-MS and ELISA methods to detect potentially important metabolites. A number of independent samples were selected to validate the identified candidates. RESULTS We selected 15 metabolites with a view to distinguishing patients with IPD, whereas 11 were identified with an authentic standard. The selected metabolites included linoleic acid, oleic acid, phospholipids, and dehydroepiandrosterone sulfate (DHEA-S). In IPD samples, significantly higher linoleic and oleic acid (P < 0.001) and lower DHEA-S (P < 0.001) concentrations were observed, compared with controls. The area under the curve from a combination of linoleic acid, oleic acid, and DHEA-S in the validation study was 0.849 for the IPD group. CONCLUSIONS The current study provides useful information to bridge the gaps in our understanding of the metabolic alterations associated with IPD and might facilitate the characterization of patients with IPD by the use of fasting serum.

Histidine and arginine are associated with inflammation and oxidative stress in obese women

The aims of the present study were to examine the serum amino acid profiles in obese and non-obese women and investigate the relationships between the serum amino acids and inflammation and oxidative stress in a human case-control study. Serum amino acids, inflammatory biomarkers (C-reactive protein and IL-6) and oxidative biomarkers (superoxide dismutase, malondialdehyde and glutathione peroxidase) were measured and compared in 235 obese women and 217 non-obese controls. The relationships between serum amino acids and inflammatory and oxidative biomarkers were examined using multiple linear regression. Among the amino acids determined, serum histidine, arginine, threonine, glycine, lysine and serine were found to be significantly lower in obese women as compared to non-obese controls (P < 0·001). The difference was the greatest for histidine (P < 0·001). In obese women, both histidine and arginine were negatively associated with inflammation and oxidative stress. In non-obese controls, histidine was negatively associated with oxidative stress. The findings in this study indicate that the metabolism of amino acids is abnormal in obese women in whom histidine and arginine have close relationships with inflammation and oxidative stress.

The calcium-sensing receptor promotes adipocyte differentiation and adipogenesis through PPARγ pathway

Adipocyte differentiation and adipogenesis are closely related to obesity and obesity-induced metabolic disorders. The calcium-sensing receptor (CaSR) has been reported to play an antilipolytic role in human adipocyte and regulate cell differentiation in many tissues. However, the effects of CaSR on adipocyte differentiation and adipogenesis have not been clarified. In the study, we observed that activation of CaSR significantly promoted adipocyte differentiation and adipogenesis in human SW872 adipocytes. Gene expression analysis revealed that the CaSR activation increased the transcription factor proliferator-activated receptor γ (PPARγ) and its downstream genes including CCAAT element binding protein α (C/EBPα), adipose fatty acid-binding protein (aP2), and lipoprotein lipase. The activity of glycerol-3-phosphate dehydrogenase was also increased after the stimulation of CaSR. In addition, levels of cyclic AMP and calcium which have been shown to regulate PPARγ gene expression were significantly affected by the activation of CaSR. These effects could be suppressed by CaSR small interfering RNA (CaSR-siRNA). In conclusion, our findings suggest that activation of CaSR promotes differentiation and adipogenesis in adipocytes, which might be achieved by upregulating PPARγ and its downstream gene expressions. Therefore, CaSR in adipocytes may be involved in the pathogenesis of obesity by promoting adipocyte differentiation and adipogenesis.

Prenatal exposure to famine and the development of hyperglycemia and type 2 diabetes in adulthood across consecutive generations: a population-based cohort study of families in Suihua, China

BACKGROUND There has been increased recognition that prenatal or perinatal nutrition has an effect on the development of type 2 diabetes (T2D) in adulthood, although studies that have directly examined whether the effect could be transmitted to the next generation remain sparse. OBJECTIVE We investigated the role of prenatal exposure to the Chinese famine in affecting future T2D risk in adulthood in 2 consecutive generations. DESIGN A total of 1034 families, including 2068 parents [parental generation (F1)] and 1183 offspring [offspring generation (F2)], were recruited from the Suihua rural area that was affected by the Chinese Famine of 1959-1961. Participants born between 1 October 1959 and 30 September 1961 were defined as famine exposed, and those born between 1 October 1962 and 30 September 1964 were defined as nonexposed. The F2 were classified as having 1) no parent exposed to famine, 2) only a mother exposed to famine, 3) only a father exposed to famine, or 4) both parents exposed to famine. Classical risk factors for T2D as well as fasting-glucose- and oral-glucose-tolerance tests were measured in both the F1 and F2. RESULTS Prenatal exposure to famine was associated with elevated risks of hyperglycemia (multivariable-adjusted OR: 1.93; 95% CI: 1.51, 2.48) and T2D (OR: 1.75; 95% CI: 1.20, 2.54) in adulthood in F1. Furthermore, compared with the offspring of nonexposed parents, the F2 with exposed parents- especially both exposed parents-had increased hyperglycemia risk (OR: 2.02; 95% CI: 1.12, 3.66) in adulthood. CONCLUSION Prenatal exposure to famine remarkably increases hyperglycemia risk in 2 consecutive generations of Chinese adults independent of known T2D risk factors, which supports the notion that prenatal nutrition plays an important role in the development of T2D across consecutive generations of Chinese adults. This trial was registered at www.chictr.org.cn as ChiCTR-ECH-13003644.

Lack of association between TNF 238 G/A polymorphism and type 2 diabetes: a meta-analysis

The aim of this meta-analysis was to determine the nature of the association between TNF 238 G/A polymorphism and the risk for T2D. We searched databases updated on January 2009 for all publications on the association between this variation and T2D. Data on genotypes and the numbers of cases and controls were assessed using Review Manager 4.2. Meta-analysis of the overall and specific populations was conducted, and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the fixed-effect model. I2 statistic was calculated to examine heterogeneity, and publication bias was evaluated by Egger test. The overall OR (95% CI) for AA and GA genotypes versus GG genotype for TNF-α-238 was 1.15 (0.92–1.44), which in European and Asian populations were 1.18 (0.92–1.51) and 1.13 (0.62–2.04), respectively. This first meta-analysis of data from the current and published studies did not detect any association between the polymorphism of TNF 238 G/A and risk for T2D.

Activated glucose-6-phosphate dehydrogenase is associated with insulin resistance by upregulating pentose and pentosidine in diet-induced obesity of rats.

Recent studies have shown that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme for the pentose phosphate pathway, was involved in insulin resistance via reduced nicotinamide adenine dinucleotide phosphate, while the roles of pentose were not examined. In the present study, the association of G6PD, pentose, and pentosidine with insulin resistance was investigated in diet-induced obesity of rats. Male Wistar rats were fed a high-fat diet for 6 weeks to generate obesity-prone (OP, n=14) and obesity-resistant (OR, n=14) rats. The levels of G6PD, pentose, and pentosidine, and oxidative stress were analyzed in serum and tissues. The OP rats, compared to the OR and control rats, had a significant increase in body weight (16.2% and 12.8%), serum triglyceride (43.4% and 12.3), and free fatty acids (49.5% and 23.6%), and developed marked insulin resistance. G6PD activities were increased in the pancreas and liver with upregulated pentose levels in serum, pancreas, and liver of OP rats. Pentosidine levels were increased only under the condition of high pentose levels and oxidative stress status in serum and pancreas of OP rats. G6PD activities in pancreas and liver, pentose levels in serum, pancreas, and liver, and pentosidine levels in serum and pancreas were positively correlated with homeostasis model of assessment-insulin resistance. Our results suggest that the upregulation of G6PD causes an increase in the accumulation of pentose and pentosidine, which might be associated with insulin resistance in the condition of obesity.

Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial

Our previous studies have shown that mangiferin decreased serum triglycerides and free fatty acids (FFAs) by increasing FFAs oxidation in both animal and cell experiments. This study sought to evaluate the effects of mangiferin on serum lipid profiles in overweight patients with hyperlipidemia. Overweight patients with hyperlipidemia (serum triglyceride ≥ 1.70 mmol/L, and total cholesterol ≥ 5.2 mmol/L) were included in this double-blind randomized controlled trial. Participants were randomly allocated to groups, either receiving mangiferin (150 mg/day) or identical placebo for 12 weeks. The lipid profile and serum levels of mangiferin, glucose, L-carnitine, β-hydroxybutyrate, and acetoacetate were determined at baseline and 12 weeks. A total of 97 participants completed the trial. Compared with the placebo control, mangiferin supplementation significantly decreased the serum levels of triglycerides and FFAs, and insulin resistance index. Mangiferin supplementation also significantly increased the serum levels of mangiferin, high-density lipoprotein cholesterol, L-carnitine, β-hydroxybutyrate, and acetoacetate, and increased lipoprotein lipase activity. However, there were no differences in the serum levels of total cholesterol, low-density lipoprotein cholesterol, serum glucose, and insulin between groups. Mangiferin supplementation could improve serum lipid profiles by reducing serum triglycerides and FFAs in overweight patients with hyperlipidemia, partly due to the promotion of FFAs oxidation.