Lycium barbarum Polysaccharides Improved Glucose Metabolism in Prediabetic Mice by Regulating Duodenal Contraction.

Lycium barbarum polysaccharides (LBPs) have been shown to exert an antiglycemic effect. Emerging evidence suggests that patients with hyperglycemia have a hypercontractility of duodenum, and targeting duodenal contraction of duodenum can be beneficial to glucose metabolism. However, it is unknown whether LBPs can improve glucose metabolism by regulating the hypercontractility of the duodenum. Our aim was to explore the effect of LBPs on duodenal contraction in prediabetic mice and also preliminarily investigate the mechanism. The results showed that LBPs improved glucose homeostasis by decreasing the duodenal amplitude of contraction rather than frequency. Moreover, LBPs ameliorated the gut microbiota composition and the levels of short-chain fatty acids, especially acetic acid, which might bind to the receptor on neurons to regulate the contraction of the duodenum. Acetic acid was hypothesized to play a key role in the above process. Then, acetic acid was determined to exert an antiglycemic effect as expected. In conclusion, LBPs may rely on acetic acid to regulate duodenal contraction to ameliorate glucose metabolism in prediabetic mice, which provides a new therapeutic strategy to treat dysglycemia.

Fat-to-muscle ratio as a predictor for dyslipidaemia in transitional-age youth.

BACKGROUND: Although dyslipidaemia may have a crucial impact on cardiovascular health in adults, there is a lack of specific data in transitional-age youth. Therefore, this study attempted to evaluate the association of dyslipidaemia with fat-to-muscle ratio (FMR), and establish FMR thresholds for diagnosing dyslipidaemia in transitional-age youth. METHODS: One thousand six hundred sixty individuals aged 16 to 24 years from the baseline of a subcohort in the Northwest China Natural Population Cohort: Ningxia Project were analysed. Anthropometric characteristics were gauged by a bioelectrical impedance analyser, and dyslipidaemia components were measured using a Beckman AU480 chemistry analyser. Additionally, this study used logistic regression to estimate the risk of dyslipidaemia based on FMR quintiles, and calculate the gender-specific ideal cut-off values of dyslipidaemia and its components by the receiver operating characteristic (ROC) curve. RESULTS: Of the 1660 participants, aged 19.06 ± 1.14 years, 558 males and 1102 females. The prevalence of dyslipidaemia was 13.4% and was significantly associated with FMR quintiles among all participants (P < 0.05). The ideal values of FMR in diagnosing dyslipidaemia were 0.2224 for males and 0.4809 for females, while males had a higher AUC than females (0.7118 vs. 0.6656). Meanwhile, high FMR values were significantly associated with adverse outcomes of dyslipidaemia, hypercholesterolemia and hypertriglyceridaemia (P < 0.05). CONCLUSIONS: The FMR was positively correlated with the prevalence of dyslipidaemia. The FMR can be used as an effective body composition index for diagnosing dyslipidaemia, especially in males, and preventive strategies should be initiated in transitional-age youth to decrease obesity-related dyslipidaemia.

Supplementation of Lycium barbarum Polysaccharide Combined with Aerobic Exercise Ameliorates High-Fat-Induced Nonalcoholic Steatohepatitis via AMPK/PPARα/PGC-1α Pathway.

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD). Either Lycium barbarum polysaccharide (LBP) or aerobic exercise (AE) has been reported to be beneficial to hepatic lipid metabolism. However, whether the combination of LBP with AE improves lipid accumulation of NASH remains unknown. Our study investigated the influence of 10 weeks of treatment of LBP, AE, and the combination (LBP plus AE) on high-fat-induced NASH in Sprague-Dawley rats. The results showed that LBP or AE reduced the severity of the NASH. LBP plus AE treatment more effectively ameliorated liver damage and lowered levels of serum lipid and inflammation. In addition, the combination can also regulate genes involved in hepatic fatty acid synthesis and oxidation. LBP plus AE activated AMPK, thereby increasing the expression of PPARα which controls hepatic fatty acid oxidation and its coactivator PGC-1α. Our study demonstrated the improvement of LBP plus AE on NASH via enhancing fatty acid oxidation (FAO) which was dependent on AMPK/PPARα/PGC-1α pathway.

Lycium barbarum Polysaccharides Promotes Mitochondrial Biogenesis and Energy Balance in a NAFLD Cell Model.

OBJECTIVE: To explore the protective effect and underlying mechanism of Lycium barbarum polysaccharides (LBP) in a non-alcoholic fatty liver disease (NAFLD) cell model. METHODS: Normal human hepatocyte LO2 cells were treated with 1 mmol/L free fatty acids (FFA) mixture for 24 h to induce NAFLD cell model. Cells were divided into 5 groups, including control, model, low-, medium- and high dose LBP (30,100 and 300 µg/mL) groups. The monosaccharide components of LBP were analyzed with high performance liquid chromatography. Effects of LBP on cell viability and intracellular lipid accumulation were assessed by cell counting Kit-8 assay and oil red O staining, respectively. Triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), adenosine triphosphate (ATP) and oxidative stress indicators were evaluated. Energy balance and mitochondrial biogenesis related mRNA and proteins were determined by quantitative real-time polymerase chain reaction and Western blot, respectively. RESULTS: Heteropolysaccharides with mannose and glucose are the main components of LBP. LBP treatment significantly decreased intracellular lipid accumulation as well as TG, ALT, AST and malondialdehyde levels (P<0.05 or P<0.01), increased the levels of superoxide dismutase, phospholipid hydroperoxide glutathione peroxidase, catalase, and ATP in NAFLD cell model (P<0.05). Meanwhile, the expression of uncoupling protein 2 was down-regulated and peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor 1/mitochondrial transcription factor A pathway was up-regulated (P<0.05). CONCLUSION: LBP promotes mitochondrial biogenesis and improves energy balance in NAFLD cell model.

Effect of Lycium barbarum polysaccharide supplementation in non-alcoholic fatty liver disease patients: study protocol for a randomized controlled trial.

BACKGROUND: Non-alcohol fatty liver disease (NAFLD) is the most common chronic liver disease in the world, with a high incidence and no effective treatment. At present, the targeted therapy of intestinal microbes for NAFLD is highly valued. Lycium barbarum polysaccharide (LBP), as the main active ingredient of Lycium barbarum, is considered to be a new type of prebiotic substance, which can improve NAFLD by regulating the gut microbiota. The purpose of this study is to evaluate the safety and efficacy of LBP supplementation in modulating gut microbiota for NAFLD patients. METHODS: This randomized, double-blind, placebo-control study will be conducted in the physical examination center of the Ningxia Hui Autonomous Region People's Hospital. A total of 50 patients with NAFLD confirmed by abdominal ultrasound, laboratory tests, and questionnaire surveys will be recruited and randomly assigned into the control group (maltodextrin placebo capsules) and the intervention group (LBP supplementation capsules) for 3 months. Neither patients, nor investigators, nor data collectors will know the contents in each capsule and the randomization list. The primary outcome measure is the level of ALT concentration relief after the intervention. Secondary outcomes include gut microbiota abundance and diversity, intestinal permeability, patient's characteristic demographic data and body composition, adverse effects, and compliance from patients. DISCUSSION: LBPs are potential prebiotics with the property of regulating host gut microbiota. Our previous studies have documented that LBP supplement can improve the liver damage and the gut microflora dysbiosis in NAFLD rats. This treatment would provide a more in-depth understanding of the effect of this LBP supplementation. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000034740 . Registered on 17 July 2020.

Lycium barbarum polysaccharide combined with aerobic exercise ameliorated nonalcoholic fatty liver disease through restoring gut microbiota, intestinal barrier and inhibiting hepatic inflammation.

Gut microbiota and intestinal permeability have been demonstrated to be the key players in the gut-liver cross talk in nonalcoholic fatty liver disease (NAFLD). Lycium barbarum polysaccharides (LBPs), which seem to be a potential prebiotic, and aerobic exercise (AE) have shown protective effects on NAFLD. However, their combined effects on intestinal microecology remain unclear. This study evaluated the effects of LBP, AE, and its combination (LBP + AE) on gut microbiota composition, intestinal barrier, and hepatic inflammation in NAFLD. LBP + AE showed high abundance and diversity of gut microbiota, restored the gut microbiota composition, increased some Bacteroidetes, short chain fatty acids, but decreased Proteobacteria and the ratio of Firmicutes/Bacteroidetes. Simultaneously, LBP, AE, and LBP + AE could restore the colonic and ileum tight junctions by increasing the expression of zonula occludens-1 and occludin. They also downregulated gut-derived lipopolysaccharides (LPSs), hepatic LPS-binding proteins, inflammatory factors, and related indicators of the LPS/TLR4/NF-κB signaling pathway for the liver. Our results implied that LBP could be considered a prebiotic agent, and LBP + AE might be a promising treatment for NAFLD because it could maintain gut microbiota balance, thereby restoring intestinal barrier and exerting hepatic benefits.

Optimised anthropometric indices as predictive screening tools for metabolic syndrome in adults: a cross-sectional study.

OBJECTIVES: We aimed to evaluate the association between metabolic syndrome (MetS) and two latest optimised indices, waist divided by height 0.5 (WHT.5R) and body mass index (BMI) multiply by the square root of BMI and waist circumference (BMI√WC), and to comprehensively compare the ability of 10 anthropometric indices to identify MetS, including BMI√WC, WHT.5R, abdominal volume index (AVI), waist-to-height ratio (WHtR), Body Roundness Index (BRI). DESIGN: Cross-sectional study. SETTING: Ningxia, China. PARTICIPANTS: A total of 3860 adults aged 18-88 years from Ningxia, China were recruited by a single stratified cluster random sampling method. METHODS: ORs and 95% CIs for associations between indices and MetS were calculated using binary logistic regression, and areas under the receiver operating characteristic (ROC) curves (AUCs) were performed to compare their predictive capacity for MetS. All results for men and women were analysed and presented separately. RESULTS: The highest adjusted ORs for MetS were observed for the following indices: AVI (OR 15.22, 95% CI 10.88 to 21.30), WHT.5R (OR 13.83, 95% CI 9.89 to 19.35) and BMI√WC (OR 12.14, 95% CI 8.79 to 16.76) in men, whereas BRI, WHtR (both OR 14.91, 95% CI 10.39 to 21.4), WHT.5R (OR 14.22, 95% CI 9.96 to 20.29) and AVI (OR 14.03, 95% CI 9.91 to 19.87) in women. In ROC analysis, AVI (AUC: 0.767 for men and 0.749 for women) and WHT.5R (AUC: 0.761 for men and 0.747 for women) showed the highest predictive ability for MetS. CONCLUSIONS: BMI√WC and WHT.5R were significantly positively associated with MetS, and AVI and WHT.5R could be useful screening tools for identifying MetS in both sexes.

An iodine balance study to explore the recommended nutrient intake of iodine in Chinese young adults.

Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the 'iodine overflow' hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 µg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 µg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for µg/d data) and retention (r 0·304 for µg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted ('overflow') through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 µg/d) might be adequate in males, the corresponding level of 61·6 µg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 µg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the 'iodine overflow' hypothesis.

Combined effect of FTO and MC4R gene polymorphisms on obesity in children and adolescents in Northwest China: a case-control study.

BACKGROUND AND OBJECTIVES: Fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes associated with obesity have been identified through Genome-wide Association Studies. However, no multiple loci interaction studies have been conducted in the Chinese population. This study investigated whether the combined effects of FTO and MC4R increase the risk of obesity in children and adolescents living in Northwest China. METHODS AND STUDY DESIGN: A total of 370 subjects (170 overweight/obese and 200 normal BMI subjects according to the Working Group on Obesity in China criteria) were enrolled using the random sampling method. FTO rs9939609 and rs9935401 and MC4R rs12970134 and rs17782313 interactions were analysed through generalized multifactor dimensionality reduction, and logistic regression models were used to calculate the risk of the relationship between genotypes and obesity. RESULTS: Generalized multifactor dimensionality reduction analysis showed a significant gene-gene interaction among FTO rs9939609/MC4R rs12970134/MC4R rs17782313, with a score of 10/10 for the cross-validation consistency and 9 for the sign test (p=0.011). A 2.453-fold increased risk of obesity was observed in individuals carrying the genotypes of FTO rs9939609 TA/AA, MC4R rs12970134 GA/AA, and MC4R rs17782313 TC/CC (adjusted for age, sex, and ethnicity; 95% CI=1.12-5.37, p=0.025). CONCLUSIONS: Our results suggested that FTO rs9939609, MC4R rs12970134, and MC4R rs17782313 are strongly associated with obesity. The combined effects were highly significant on obesity in children and adolescents living in Northwest China.

Melanocortin-4 receptor rs17782313 polymorphisms are associated with serum triglycerides in older Chinese women.

BACKGROUND AND OBJECTIVES: MC4R (melanocortin-4 receptor) gene polymorphisms have been associated with serum triglycerides (TG) in Caucasians and Japanese, but no reports are available Chinese. The purpose of this study was to find whether there was an association of rs17782313 polymorphisms at the MC4R gene with serum TG in elderly Chinese. METHODS AND STUDY DESIGN: 2,012 over 40 years participated in a cross-sectional study in which their body mass index (BMI), TG, high density lipoprotein-cholesterol (HDL-C), and MC4R rs17782313 polymorphisms were determined. RESULTS: For women, carriers of the T/T genotype had significantly lower serum TG than those with C/C genotype (p=0.006). Carriers of the C/C genotype of this polymorphisms exhibited significantly lower fasting HDL-C levels compared with T/T and T/C genotypes (p=0.025), and increased glycosylated hemoglobin (HbA1c) (p=0.043), but no change in blood pressure. Higher serum TG in carriers of the C/C genotype of MC4R gene remained stable after adjustment for age, smoking, drinking, BMI, waist circumference (WC) and three or more components of the metabolic syndrome (MS) by multivariable linear regression (p=0.01) in women. The carriers of the C/C genotype of MC4R gene showed significantly greater odds ratio for TG than T/C and T/T genotypes, even when adjusted for age, smoking, drinking, BMI and WC in women. CONCLUSIONS: The rs17782313 C/C genotype is associated with higher TG levels in older Chinese women.

Anticancer effects of adenovirus-mediated calreticulin and melanoma-associated antigen 3 expression on non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is highly prevalent and needs novel therapies. Melanoma-associated antigen 3 (MAGE-A3) is a lung cancer antigen and calreticulin (CALR) can modulate immune responses. Our previous study has shown that up-regulated MAGE-A3 and CALR expression inhibits the proliferation and invasion of glioma cells. In this study, we examined the effect of adenovirus (Ad)-mediated MAGE-A3 and/or CALR expression on the proliferation, invasion, and apoptosis of human NSCLC cells and on the vascular tube formation of human endothelial cells as well as on dendritic cell (DC) activation and induced CD8(+) cytotoxic T lymphocyte (CTL) activity in vitro. We found that low levels of CALR and MAGE-A3 were expressed by A549 cells, but only very low CALR was expressed by DC. Up-regulated CALR and MAGE-A3 expression by infection with Ad-CALR/MAGE-A3 significantly inhibited the proliferation and invasion, but promoted the apoptosis of A549 cells. Up-regulated CALR and MAGE-A3 expression significantly inhibited cyclin D1 expression and the AKT, ERK1/2 and NF-κB expression and phosphorylation in A549 cells. Up-regulated CALR expression inhibited the tube formation in human endothelial cells. Up-regulated CALR and MAGE-A3 expression synergistically enhanced classical DC activation by enhancing IL-12, but reducing IL-10 secretion. Furthermore, CTLs induced by up-regulated CALR and MAGE-A3 expressing DCs synergistically triggered A549 cell apoptosis, which was abrogated by treatment with anti-HLA I, but not anti-HLA II antibodies. Moreover, CTLs induced by CALR and MAGE-A3-expressing DCs had a higher frequency of A549-specific IFN-γ-secreting T cells. Our data indicated that up-regulated CALR and MAGE-A3 expression inhibited the carcinogenesis of NSCLC by modulating the AKT, ERK MAPK and NF-κB signaling and enhanced classical DC activation and MAGE-A3-specific CTL cytotoxicity. Therefore, our findings may provide new insights in understanding the role of CALR in modulating antigen-specific T cell immunity and may aid in the design of new therapies for NSCLC.

Impact of elevated aspartate and alanine aminotransferase on metabolic syndrome and its components among adult people living in Ningxia, China.

OBJECTIVE: Metabolic syndrome (MS) is a combination of medical disorders that increase the risk for cardiovascular disease and diabetes mellitus. It suggests an association between an elevated serum aminotransferase level and MS. Little data show the relationship between the levels of serum aminotransferase and the incidence of MS in Ningxia, China. METHODS: A total of 5415 subjects who received medical health checkups from 2007 to 2009 were enrolled in the study. The participants were interviewed by trained health workers under a structured questionnaire. MS was defined according to the modified ATPIII criteria for Asian Americans by the American Heart Association (AHA-ATP III). RESULTS: The prevalence of elevated aspartate aminotransferase (AST) and ALT (>40 U/L) were 7.1% and 22.2% in males, and 2.1% and 4.8% in females respectively. The prevalence of MS was 32.1% in males and 15.4% in females. The components of MS were significantly more in the group with elevated aminotransferase levels than in the group with normal aminotransferase levels. The odds ratios (95% CI) for elevated AST were 1.90 (1.49, 2.42), 2.59 (2.01, 3.39), 1.68 (1.32, 2.15), and 1.81 (1.36, 2.42) in the adults with abdominal obesity, high serum triglycerides levels, high blood pressure, and high plasma glucose levels respectively. After adjustment for age, the odds ratios (95% CI) for elevated ALT were 3.08 (2.63, 3.61), 4.30 (3.64, 5.08), 1.26 (1.08, 1.48), 2.16 (1.93, 2.65) and 2.38 (1.96, 2.87) in adults with abdominal obesity, high serum triglycerides levels, low serum high-density lipoproteincholesterol (HDL-C), high blood pressure, and high plasma glucose levels respectively. The odds ratios (95% CI) for elevated AST were 1.67 (1.06, 2.63), 2.28 (1.46, 3.63), 2.59 (1.59, 4.21) and for elevated ALT 2.02 (1.50, 2.73), 2.68 (1.96, 3.65), 3.94 (2.86, 5.43) for the subjects with 1, 2, and ≥3 risk factors after adjustment for age, gender, and BMI. CONCLUSION: The serum aminotransferase levels were higher in males compared to females, and serum ALT level was more closely associated with MS than the AST level in adults in Ningxia, China. With an increasing the number of components of MS, the aminotransferase levels and the risks for elevated aminotransferase increase, whereas the AST/ALT ratios decrease.

[Relationship of ionized calcium and 25-(OH) D in serum with obesity].

OBJECTIVE: To investigate the relationship of ionized calcium and 25-(OH) D level in serum with obesity in order to provide theoretical basis for preventing obesity-related diseases. METHODS: Base on a cross-sectional study, 169 overweight/obese subjects (92 men: age (37.76 +/- 17.56) years, 77 women: age (38.79 +/- 17.40) years) and 169 normal weight control subjects (92 men: age (36.24 +/- 17.28) years, 77 women: age (32.32 +/- 13.07) years) were selected in a 1:1 case-control matches. 25-(OH) D was assessed by ELISA. Serum ionized calcium was measured by flame atomic absorption spectrophotometry. The relationship of ionized calcium and 25-(OH) D level in serum with obesity was analyzed by using a Logistic regression model. RESULTS: The average serum ionized calcium in overweight or obese subjects was(46.9 +/- 20.7) mg/L and that in normal control subjects was (63.2 +/- 19.5) mg/L (P < 0.001). Serum 25-(OH) D of overweight or obese was lower than normal control subjects ((48.3 +/- 16.7) nmmol/L vs. (63.8 +/- 35.4) nmmol/L, P < 0.001). Serum ionized calcium and 25-(OH) D was independently associated with body mass index in a logistic regression model [OR = 0.959, 95% CI 0.945-0.973; OR = 0.435, 95% CI 0.329-0.575]. CONCLUSION: Serum 25-(OH) D levels in obesity group was lower than that in control group. The results suggest that vitamin D might play an important role in the risk of developing obesity.