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Vitamin D is found involved in glucose metabolism in recent years. Vitamin D deficiency is very common especially in children. Whether vitamin D deficiency in early life affects adult diabetes...

Background Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the association of different vitamin D intervention methods and outdoor activity on the vitamin D status of children in North China. Methods In this observational study, a total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D intervention (either prescribed by physicians or given by parents) and outdoor activity were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem–mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D intervention or outdoor activity with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons. Results The overall rate of hypovitaminosis D was 65.60%. Of the children’s outdoor activity, 35.63, 31.95, and 32.42% were below 30 min/d, 30–60 min/d and over 60 min/d, respectively. Furthermore, the proportion of therapeutic intervention, supplementation intervention and no vitamin D intervention among the children was 16.48, 32.87, and 50.65%, respectively. After adjusted for confounding factors, vitamin D intervention was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with therapeutic doses and 0.423 (0.404, 0.443) in those with supplementation doses, compared with children without vitamin D intervention. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30–60 min/d], independent of vitamin D intervention. Conclusions High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D intervention and outdoor activity are all negatively associated with children’s vitamin D deficiency. Routine vitamin D intervention combined with increased outdoor time might be an effective approach to prevent hypovitaminosis D among children, especially those at school, living at high latitudes.

Collagen from fish has been proven to have a low antigenicity that has no difference in the genetic codes compared with mammalian-based collagen. This study was designed to investigate the impact of tilapia skin collagen on immunogenicity and biocompatibility in vivo and in vitro. The structural characteristics of both acid-soluble and pepsin-soluble collagen (ASC and PSC), determined using SDS-PAGE and atomic force microscopy imaging experiments, revealed that the collagen had the basic characteristics of type I collagen (COL-I). The in vitro biocompatibility of the collagens showed good cell proliferation against human foreskin fibroblast (HFF-1) cells. PSC and ASC were considered to be almost non-hemolytic biomaterials with favorable blood compatibility in hemolysis tests. The in vivo antigenicity of the collagen in an ICR mouse model evoked an acceptable specific inflammatory response compared to bovine collagen. The implant’s position had developed a complete granulation tissue and the sponge disappeared after 8 weeks. The level of cytokines produced by the COL-I immune response was much lower than bovine collagen, which indicated the appropriate implantable property and biodegradability of the collagens. In conclusion, the tilapia COL-I has a lower immunogenicity with better compatibility than bovine COL-I and is a potential alternative to conventional mammalian collagens in biomedical uses.

The liver is directly connected to the intestines through the portal vein, which enables the gut microbiota and gut-derived products to influence liver health. There is accumulating evidence of decreased gut flora diversity and alcohol sensitivity in patients with various chronic liver diseases, including non-alcoholic/alcoholic liver disease, chronic hepatitis virus infection, primary sclerosing cholangitis and liver cirrhosis. Increased intestinal mucosal permeability and decline in barrier function were also found in these patients. Followed by bacteria translocation and endotoxin uptake, these will lead to systemic inflammation. Specific microbiota and microbiota-derived metabolites are altered in various chronic liver diseases studies, but the complex interaction between the gut microbiota and liver is missing. This review article discussed the bidirectional relationship between the gut and the liver, and explained the mechanisms of how the gut microbiota ecosystem alteration affects the pathogenesis of chronic liver diseases. We presented gut-microbiota targeted interventions that could be the new promising method to manage chronic liver diseases.

Background: Vitamin D deficiency is a major public health problem in China while there are seldom reports about vitamin D nutrition status in Chinese college students. The purpose of this study is to explore the vitamin D status of the college freshmen who came from different provinces of China and to comprehensive analyze the effects of diet, physical activity, and UV protection on serum vitamin D levels. Methods: Totally 1,667 freshmen who came from 26 provinces, autonomous districts or municipalities, were recruited into this study. An online questionnaire was used to collect the information including demographic status, diet habit, physical activity, and UV protection of the participants. Serum 25(OH)D3 concentrations were measured using a liquid chromatograph mass spectrometer. Multivariate linear regression analyses were used to explore the comprehensive influence of diet, physical activity, and UV protection on serum 25(OH)D3 levels. Results: The average age of the subjects was18.55±0.90 years, with 23.0% male and 77.0% female. The mean serum 25(OH)D3 was 18.06±6.34ng/mL and the proportion of vitamin D deficiency and insufficiency was 67.5% and 27.8%, respectively. Multivariate linear regression indicated that milk and yogurt intake≥200mL/d, calcium or vitamin D supplements and average time of outdoor activity ≥60 min/day were positively linked to higher serum vitamin D while sweets intake ≥10g/d and higher UV protection index were negatively influenced serum vitamin D after adjusted for age, gender, students’ original residence, latitudes and longitude. Conclusions: Vitamin D deficiency is an important health problem in Chinese college students. Milk and yogurt intake and outdoor activity should be encouraged while sweets intake should be limited for preventing vitamin D deficiency. Public health policies should consider well-balanced guidelines on UV protection and vitamin D food fortification or supplementation.

Background: Typical pseudogenes expressions have been reported to been associated with liver diseases. However, whether pseudogenes contribute to non-alcoholic fatty liver disease (NAFLD) and triglyceride (TG) accumulation and the underlying molecular mechanisms are poorly understood. We aimed to elucidate the role of Gm12664-201 in TG accumulation and the potential mechanism.Method and Results: We identified Gm12664-01 in high-fat diet (HFD) fed mice using microarray and confirmed its expression in both vivo and vitro high fat models with quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then changed the level of Gm12664-201 in vitro to determine the role of it in TG accumulation, which evaluated by Oil red O staining and enzymatic method. The underlying mechanisms of Gm12664-01 in TG accumulation were investigated by detecting signaling markers BiP, PERK, ATF6, CHOP, eIF2α, XBP1 and ATF4 with qRT-PCR and western blotting. We found that Gm12664-201 was markedly increased in liver tissue of HFD mice and steric acid (SA) incubated AML-12 cells. Gm12664-201 overexpression rendered AML-12 cells susceptible to triglyceride (TG) accumulation, and silencing pseudogene Gm12664-201 expression efficiently alleviated SA-induced TG accumulation. Further studies revealed that Gm12664-201 regulates endoplasmic reticulum stress signaling markers BiP, PERK, ATF6, CHOP, eIF2α, XBP1 and ATF4 expression, which may be responsible for increased TG accumulation in hepatocytes.Conclusions: Upregulation of pseudogene Gm12664-201 induced by HFD promotes triglyceride accumulation and activates ER stress pathway in hepatocytes.

The aim was to systematically analyse the association of the specific flavonoids, Mg and their interactions from different food sources with the metabolic syndrome (MetS) and its components in a cohort study. A total of 6417 participants aged 20 to 74 years from the Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases were included. Multivariate logistic regression analyses, forest plot and restricted cubic spline were performed in the study. After a 5·3-year follow-up, 1283 incident cases of the MetS were reported. Those with a higher total flavonoid intake had a lower risk of the MetS (fourth v. first quartile, relative risk (RR) 0·58; 95 % CI 0·37, 0·93; P = 0·024) and central obesity (RR 0·56; 95 % CI 0·33, 0·95; P = 0·032). Further analysis showed that the specific flavonoids quercetin, kaempferol, isorhamnetin, luteolin, and flavonoids from fruits, potatoes and legumes had the similar associations with risk of the MetS and central obesity (P < 0·05 for all). A higher intake of total flavonoids, quercetin and luteolin combined with a high level of Mg was more strongly associated with a lower risk of the MetS (RR 0·60; 95 % CI 0·45, 0·81 for total; RR 0·61; 95 % CI 0·45, 0·82 for quercetin; RR 0·52; 95 % CI 0·38, 0·71 for luteolin; all Pfor interaction < 0·01). Dose–response effects showed an L-shaped curve between the total intake of five flavonoids and the risk of the MetS. A higher flavonoid intake is associated with a lower risk of the MetS and central obesity; their combination with Mg helps to strengthen their negative association with the MetS.

Background: Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the association of different vitamin D intervention methods and outdoor activity on the vitamin D status of children in North China. Methods: In this observational study, a total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D intervention (either prescribed by physicians or given by parents) and outdoor activity were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem–mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D intervention or outdoor activity with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons.Results: The overall rate of hypovitaminosis D was 65.60%. Of the children’s outdoor activity, 35.63%, 31.95%, and 32.42% were below 30min/d, 30-60 min/d and over 60min/d, respectively. Furthermore, the proportion of therapeutic intervention, supplementation intervention and no vitamin D intervention among the children was 16.48%, 32.87%, and 50.65%, respectively. After adjusted for confounding factors, vitamin D intervention was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with therapeutic doses and 0.423 (0.404, 0.443) in those with supplementation doses, compared with children without vitamin D intervention. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30–60 min/d], independent of vitamin D intervention. Conclusions: High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D intervention and outdoor activity are all negatively associated with children’s vitamin D deficiency. Routine vitamin D intervention combined with increased outdoor time might be an effective approach to prevent hypovitaminosis D among children, especially those at school, living at high latitudes.

Background: Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the effect of different vitamin D intervention methods and outdoor activity on the vitamin D status of children in North China. Methods: A total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D intervention, and outdoor activity were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem–mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D intervention or outdoor activity with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons.Results: The overall rate of hypovitaminosis D was 65.60%. Of the children’s outdoor activity, 35.63%, 31.95%, and 32.42% were below 30min/d, 30-60 min/d and over 60min/d, respectively. Furthermore, the proportion of therapeutic intervention, supplementation intervention and no vitamin D intervention among the children was 16.48%, 32.87%, and 50.65%, respectively. After adjusted for confounding factors, vitamin D intervention was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with therapeutic doses and 0.423 (0.404, 0.443) in those with supplementation doses, compared with children without vitamin D intervention. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30–60 min/d], independent of vitamin D intervention. Conclusions: High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D intervention and outdoor activity are all negatively associated with children’s vitamin D deficiency. Routine vitamin D intervention combined with increased outdoor time might be an effective approach to prevent hypovitaminosis D among children, especially those at school, living at high latitudes.

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Objective:To investigate the knowledge, attitudes and practices (K-A-P) about food safety and nutrition in Chinese adults who were recruited to the online survey during the epidemic of corona virus disease 2019 (COVID-19).Design:Participants were recruited by an online snowball sampling method. An electronic questionnaire was sent to our colleagues, students, friends, other professionals and their referrals helped us recruit more participants. The questionnaire included socio-demographic information, the attention paid to COVID-19, K-A-P about food safety and nutrition. Multiple and logistic regression analyses were used to explore related factors of K-A-P.Subjects:Totally, 2272 participants aged 24·09 ± 9·14 years, from twenty-seven provinces, autonomous districts or municipalities, with 18·3 % male and 83·4 % with a medical background.Results:The total possible knowledge score was 8·0, the average score was 5·2 ± 1·6 and 4·2 % obtained 8·0. The total possible attitudes score was 8·0, the average score was 6·5 ± 1·4 and 36·1 % obtained 8·0. The total possible food safety practices score was 5·0, the average score was 3·7 ± 1·0 and 20·7 % obtained 5·0. During this public emergency, 79·4 % participants changed diet habits, including increasing vegetables, fruit and water intake and reducing sugary drinks and snacks. Gender, age, educational and professional background, disease history, the attention paid to COVID-19 and related knowledge were associated with K-A-P.Conclusion:There was room for the improvement of K-A-P in participants during this public health emergency and further strengthening education about food safety and nutrition is needed. Findings indicate that education should address biased or misleading information and promote nutritious food choices and safe food practices.

Background Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the effect of different supplementation methods and outdoor activity time on the vitamin D status of children in North China. Methods A total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D supplementation, and outdoor time were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem–mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D supplementation or outdoor time with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons. Results The overall rate of hypovitaminosis D was 65.60%. Of the children’s outdoor time, 35.63%, 31.95%, and 32.42% were below 30 min/d, 30–60 min/d and over 60 min/d, respectively. Furthermore, the proportion of iatrogenic supplementation, voluntary supplementation and no vitamin D supplementation among the children was 16.48%, 32.87%, and 50.65%, respectively. After adjusted for confounding factors, vitamin D supplementation was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with iatrogenic supplementation and 0.423 (0.404, 0.443) in those with voluntary supplementation, compared with children without vitamin D supplementation. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30–60 min/d], independent of vitamin D supplementation. Conclusions High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D supplementation and outdoor time are all negatively associated with children’s vitamin D deficiency. Routine 25(OH)D testing combined with vitamin D supplementation might be an effective approach to prevent hypovitaminosis D among children living at high latitudes.

OBJECTIVES: To explore whether lower outdoor temperature increases cardio-cerebrovascular disease risk through regulating blood pressure and whether indoor heating in winter is beneficial to prevent cardio-cerebrovascular disease in cold areas. METHODS: We analyzed the data of 38 589 participants in Harbin from the China Kadoorie Biobank (CKB) during 2004-2008, with an average of 7.14-year follow-up. Linear regression analysis was performed to estimate the relationship between outdoor temperature and blood pressure. Cox regression analysis and logistic regression analysis were used to analyze the association of blood pressure with cardio-cerebrovascular event risk. Mediation analysis was performed to explore the role of blood pressure in the association between outdoor temperature and cardio-cerebrovascular events risk. RESULTS: There was an increase of 6.7 mmHg in SBP and 2.1 mmHg in DBP for each 10 °C decrease in outdoor temperature when outdoor temperature was higher than 5 °C. There was an inverse association between outdoor temperature and cardio-cerebrovascular event morbidity. The increases in blood pressure and cardio-cerebrovascular event morbidity were attenuated in months when central heating was fully provided. Participants with hypertension have higher risks of cardio-cerebrovascular disease (hazard ratio 1.347; 95% CI 1.281--1.415), CVD (hazard ratio 1.347; 95% CI 1.282--1.416), MACE (hazard ratio 1.670; 95% CI 1.560--1.788) and stroke (hazard ratio 1.683; 95% CI 1.571--1.803). Mediation analysis demonstrated that the association between outdoor temperature and cardio-cerebrovascular events risk was potentially mediated by blood pressure. CONCLUSION: Temperature-driven blood pressure potentially mediates the association between outdoor temperature and cardio-cerebrovascular events risk. Indoor heating in winter is probably beneficial to cardio-cerebrovascular disease prevention by inhibition of blood pressure increase.

Although hyperuricemia and obesity are significantly correlated, their temporal relationship and whether this relationship is associated with future risk of diabetes are largely unknown. This study examined temporal relationship between hyperuricemia and obesity, and its association with future risk of type 2 diabetes. This study examined two longitudinal cohorts totally including 17,044 subjects from China with an average of 6.0 years follow-up. Measurements of body mass index (BMI), waist circumference (WC), percentage of body fat and fasting serum uric acid were obtained at two time points. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between hyperuricemia and obesity, and the association of this temporal relationship with follow-up diabetes. In combined data of the two cohorts, the cross-lagged path coefficient (β1 = 0.121; 95% confidence interval (CI): 0.108–0.135) from baseline uric acid to the follow-up BMI was significantly greater than the path coefficient (β2 = 0.055, 95% CI: 0.038–0.072) from baseline BMI to the follow-up uric acid (P = 8.14e−10 for the difference between β1 and β2) with adjustment for covariates. The separate cross-lagged path models of uric acid with WC and percentage of body fat showed temporal patterns similar to that noted for uric acid with BMI. Further, the path coefficient (β1) from baseline uric acid to follow-up BMI in the group with diabetes was significantly greater than without diabetes (P = 0.003 for the difference of β1s in the two groups). BMI partially mediated the association of uric acid with risk of diabetes, and the percentage of mediated-association was estimated at 20.3% (95% CI: 15.7–24.8%). Results of these analyses in the combined data were consistent with those in the two cohorts, respectively. These findings indicated that increased uric acid levels probably associated with obesity and type 2 diabetes, and more definite research is needed to define any role for uric acid in relation to these diseases.

Increasing circulating Ca2+ levels within the normal range has been reported to positively correlate with the incidence of fatal cardiovascular diseases (CVDs). However, limited studies have been able to delineate the potential mechanism(s) linking circulating Ca2+ to CVD. In this study, we exposed primary human umbilical vein endothelial cells (HUVECs) and human umbilical vein cell line (EA.hy926) to different extracellular Ca2+ to mimic the physiological state. Our data revealed that increasing extracellular Ca2+ significantly enhanced susceptibility to tumor necrosis factor (TNF)-alpha-stimulated vascular cell adhesion molecule (VCAM)-1 expression and monocytes adhesion. Knocking-down VCAM-1 by siRNA abolished calcium-induced monocytes adhesion on HUVECs. Follow up mechanistic investigations identified that extracellular Ca2+-increased calcium influx contributed to the activation of VCAM-1. This was mediated via upregulation of transient receptor potential channel (TRPC)1 in a nuclear factor (NF)κB-dependent manner. Most importantly, we found that a novel TRPC1-regulated extracellular signal-regulated kinase 1/2 (ERK1/2) pathway exclusively contributed to calcium-induced NFκB activation. This study provided direct evidence that increasing extracellular Ca2+ enhanced TNF-alpha-induced VCAM-1 activation and monocytes adhesion. Moreover, we identified a novel TRPC1/ERK1/2/NFκB signaling pathway mediating VCAM-1 activation and monocyte adhesion in this pathological process. Our studies indicate that blood calcium levels should be strictly monitored to help prevent CVD, and that TRPC1 might act as a potential target for the treatment and prevention against increased circulating calcium-enhanced CVDs.

Although hyperuricemia and insulin resistance significantly correlated, their temporal sequence and how the sequence influence on future risk of hypertension are largely unknown. This study assessed temporal relationship between uric acid and insulin resistance and its impact on future risk of hypertension by examining a longitudinal cohort including 8543 subjects aged 20 to 74 years from China, with an average follow-up of 5.3 years. Measurements of fasting uric acid, as well as fasting and 2-hour serum glucose and insulin, were obtained at baseline and follow-up. Indicators of hepatic and peripheral insulin resistance were calculated. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between uric acid and insulin resistance and its impact on follow-up hypertension. After adjusting for covariates, the cross-lagged path coefficients ( β 1 values) from baseline uric acid to follow-up insulin resistance indices were significantly greater than path coefficients ( β 2 values) from baseline insulin resistance indices to follow-up uric acid ( β 1 =0.110 versus β 2 =0.017; P β 1 =−0.208 versus β 2 =−0.021; P P β 1 values in the 2 groups). Insulin resistance partially mediated the effect of uric acid on subsequent hypertension, and the mediation effect of peripheral insulin resistance was significantly greater than that of hepatic insulin resistance (31.3% versus 13.2%; P

Background: Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by excessive lipid deposition in hepatocytes, except alcohol and other definite liver damage factors. Emerging evidence indicates the involvement of long non-coding RNAs (LncRNAs) in regulating pathogenesis of NAFLD. However, the specific mechanism underlying this process still remains unclear. Objective: The aim of this study was to investigate the functional implication of lncRNA Gm12664 in the hepatic lipid accumulation of NAFLD. Methods: We applied the microarray approach to determine the differential expression profiles of lncRNAs, mRNAs and miRNAs in liver tissues of HFD-fed mice. Based on the co-expression networks between lncRNAs and lipogenesis-related genes during hepatic lipid accumulation in the pathogenesis of NAFLD, the role of LncRNA Gm12664 was further investigated and was focused on the regulation of CAV1. Besides, the miRNA microarray and bioinformatics analysis were used to predict the miRNA which might mediate the overexpression of CAV1 induced by Gm12664. In vitro and in vivo assays were performed to explore the biological effects of Gm12664 in hepatic lipid metabolism through the Gm12664/miR-295-5p/CAV1 axis. Results: We found that lncRNA Gm12664 was markedly up-regulated and promoted CAV1 expression in both livers of HFD-fed mice and FFA-treated AML-12 cells. Suppression of Gm12664 reversed FFA-induced triglyceride accumulation in AML-12 cells through down-regulation of CAV1. Further mechanistic studies demonstrated that miR-295-5p participated in the regulation of CAV1 by Gm12664 during hepatic lipid accumulation. Gm12664 positively regulated the expression of CAV1, through sponging mir-295-5p, and promoted hepatic lipid accumulation in the pathogenesis of NAFLD. Conclusion: Our data are the first to document the working model of Gm12664 functions as a potential hepatocyte lipid accumulation facilitator. Gm12664 promotes hepatic lipid accumulation by binding to miR-295-5p, and eventually regulating the up-regulation of CAV1. Our results suggest the potency of Gm12664/miR-295-5p/CAV1 axis as a promising therapeutic target for NAFLD.

Background Differential effects of individual saturated fatty acids (SFAs), particularly stearic acid (C18:0), relative to the shorter-chain SFAs have drawn interest for more accurate nutritional guidelines. However, specific biologic and pathologic functions that can be assigned to particular SFAs are very limited. The present study was designed to compare changes in metabolic and transcriptomic profiles in mice caused by a high C18:0 diet and high palmitic acid (C16:0) diet. Methods Male C57BL/6 mice were assigned to a normal fat diet (NFD), a high fat diet with high C18:0/C16:0 ratio (HSF) or an isocaloric high fat diet with a low C18:0/C16:0 ratio (LSF) for 10 weeks. An oral glucose tolerance test, 72-h energy expenditure measurement and CT scan of body fat were done before sacrifice. Fasting glucose and lipids were determined by an autobiochemical analyzer. Blood insulin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured by enzyme-linked immunosorbent assay methods. Free fatty acids (FFAs) profiles in blood and liver were determined by using gas chromatography-mass spectrometry. Microarray analysis was applied to investigate changes in transcriptomic profiles in the liver. Pathway analysis and gene ontology analysis were applied to describe the roles of differentially expressed mRNAs. Results Compared with the NFD group, body weight, body fat ratio, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, IL-6, serum and liver FFAs including total FFAs, C16:0 and C18:0 were increased in both high fat diet groups and were much higher in the HSF group than those in the LSF group. Both HSF and LSF mice exhibited distinguishable long non-coding RNA (lncRNA), microRNA and mRNA expression profiles when compared with those of NFD mice. Additionally, more differentially expressed lncRNAs and mRNAs were observed in the HSF group than in the LSF group. Some biological functions and pathways, other than energy metabolism regulation, were identified as differentially expressed mRNAs between the HSF group and the LSF group. Conclusion The high fat diet with a high C18:0/C16:0 ratio induced more severe glucose and lipid metabolic disorders and inflammation and affected expression of more lncRNAs and mRNAs than an isocaloric low C18:0/C16:0 ratio diet in mice. These results provide new insights into the differences in biological functions and related mechanisms, other than glucose and lipid metabolism, between C16:0 and C18:0.

To explore the relationship between spicy food intake and overweight or obesity in the population, and provide theoretical basis for dietary prevention of obesity.The data of this study was collected from the cross-sectional population of China Kadoorie Biobank(CKB) in Harbin from 2004 to 2008. A cluster random sampling method was used to select 57 555 subjects aged 30-79(23 254 males and 34 301 females). Demographic information and habits information such as smoking and drinking were obtained by face-to-face questionnaires. Food frequency questionnaires were used to obtain information on various foods including spicy food intake. Physical examination was used to obtain indicators of height and weight. Logistic regression method was used to analyze the influence of spicy food intake and its interaction with predilection for meat/vegetarian diet on the risk of overweight and obesity.Compared with people who intake spicy foods with low frequency, the risk of overweight and obesity in people with a high frequency of intake spicy foods increased by 29%(OR=1.285, 95%CI 1.251-1.319, P0.001) in males and 33%(OR=1.329, 95%CI 1.294-1.364, P0.001) in females. Compared with the people who intake spicy food with a slightly intensity, the risk of overweight and obesity in males and females with a extremely intensity of intake spicy foods increased by 20%(OR=1.198, 95%CI 1.137-1.259, P=0.011) and 19%(OR=1.194, 95%CI 1.141-1.247, P=0.003), respectively. In the male population, the risk of overweight and obesity was the highest among those who preferred meat and had high frequency and degree of spicy food intake. There was an interaction between meat/vegetarian preference and spicy food intake(P0.001).Intake spicy food can increase the risk of overweight and obesity, while reducing the intake of spicy foods and meats can be more effective in prevent overweight and obesity.

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.

Scope Ursolic acid (UA) is a triterpenoid compound with multifold biological functions. Our previous studies have reported that UA protects against high-fat diet-induced obesity and improves insulin resistance (IR). However, the potential mechanisms are still undefined. Free fatty acid (FFA) metabolism in skeletal muscle plays a central role in obesity and IR. Therefore, in this study, we investigated the effect and the potential mechanisms of UA on skeletal muscle FFA metabolism. Methods and results In diet-induced obese rats, 0.5% UA supplementation for 6 weeks markedly reduced body weight, increased energy expenditure, decreased FFA level in serum and skeletal muscle and triglyceride content in skeletal muscle. In vitro, the data provided directly evidence that UA significantly increased fluorescently labeled FFA uptake and 3H-labeled palmitic acid β-oxidation. UA-activated AMP-activated protein kinase (AMPK) and downstream targets were involved in the increase of FFA catabolism. Moreover, upregulated uncoupling protein 3 (UCP3) by UA contributed to AMPK activation via elevating adenosine monophosphate/adenosine triphosphate ratio. Conclusion UA increases FFA burning through enhancing skeletal muscle FFA uptake and β-oxidation via an UCP3/AMPK-dependent pathway, which provides a novel perspective on the biological function of UA against obesity and IR.

The association between dietary Mn and type 2 diabetes is unclear. We aimed to elucidate whether dietary Mn is associated with type 2 diabetes, to investigate whether this association is independent of dietary total antioxidant capacity (TAC) and to explore the underlying mechanisms in their association. Two prospective cohorts of 3350 and 7133 Chinese adults (20–74 years old) were enrolled including, respectively, 244 and 578 individuals newly diagnosed with type 2 diabetes, with mean values of 4.2 and 5.3 years of follow-up. Cox’s proportional-hazards regression and linear regression were performed to investigate the association between dietary Mn and type 2 diabetes (diagnosed by OGTT) or HbAlc and to analyse the joint association between dietary Mn and TAC. Restricted cubic spline (RCS) regression was applied to the non-linear association between dietary Mn and incidence of type 2 diabetes. Mediation analysis was applied to explore potential mediators in their association in a subgroup of 500 participants. Dietary Mn intakes were 4.58 ± 1.04 and 4.61 ± 1.08 (mean ± SD) mg/day in the two cohorts. Dietary Mn was inversely associated with type 2 diabetes incidence and HbAlc concentration in both cohorts (ptrend 6.01 and 6.10–6.97 mg/day were associated with a significantly lower type 2 diabetes incidence in the two respective cohorts. Mediation analysis showed that high plasma Mn and low oxidative stress (increased Mn superoxide dismutase and decreased 8-hydroxydeoxyguanosine) contributed to the association between dietary Mn and both type 2 diabetes and HbAlc. Dietary Mn was inversely associated with type 2 diabetes independently of TAC. In addition, this association was stronger in a high- rather than low-TAC diet. Plasma Mn and oxidative stress were mediators in the association between dietary Mn and type 2 diabetes. Future studies on absolute Mn intake should be conducted to study the potential non-linearity and optimal levels of dietary Mn and type 2 diabetes.

Background: We have demonstrated that the calcium-sensing receptor (CaSR) is involved in lipid metabolism; however, whether CaSR polymorphisms affect lipid metabolism in obesity is still unclear. The present study aimed to determine the effects of CaSR polymorphisms on HTG risk in obese Chinese. Methods: A total of 972 subjects with HTG and 1197 with normal triglyceride (NTG) were stratified by body mass index (BMI) into normal weight, overweight or obesity subgroups. After 12-h fasting, CaSR polymorphisms in exon 7 were determined in the blood. Serum lipids and glucose, as well as height, body weight and waist circumference were measured. The anthropometric and metabolic characteristics of the NTG subjects were re-evaluated 3. years later. Results: There were no genotypic or allelic distribution differences for the A986S or Q1011E polymorphisms between the NTG and HTG groups. However, the G/G genotypic and G allelic distributions of the CaSR R990G polymorphism in the HTG group were higher than the NTG group (p

BACKGROUND Several studies have focused on the effects of calcium intake on serum lipid concentrations in postmenopausal women. However, many premenopausal women are taking calcium supplements in China. To our knowledge, no studies have assessed whether the effects of calcium supplementation on blood lipids are similar between premenopausal and postmenopausal women. OBJECTIVE We assessed the effects of calcium supplementation on blood lipid concentrations in premenopausal and postmenopausal women with dyslipidemia. DESIGN A total of 190 premenopausal women (30-40 y old) and 182 postmenopausal women (50-60 y old) with dyslipidemia were given 800 mg Ca/d or a placebo for 2 y in a double-blind, randomized, placebo-controlled trial. Blood pressure, fasting glucose and serum lipid concentrations, carotid intima-media thickness (CIMT), dietary nutrient intakes, and physical activity levels were determined at baseline and after 2 y. RESULTS There was a significant interaction between calcium supplementation and menopausal status on serum cholesterol concentrations (P < 0.001) and CIMT (P = 0.017). Serum cholesterol concentrations and CIMT were significantly increased in postmenopausal women (P < 0.01) after 2 y. Serum triglyceride, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol concentrations were not affected after 2 y. CONCLUSIONS Calcium supplementation in postmenopausal women with dyslipidemia increases serum total cholesterol concentrations and CIMT. In postmenopausal women with dyslipidemia, calcium supplements should be prescribed with caution. This trial was registered at http://www.chictr.org/cn/ as ChiCTR-TRC-12002806.

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) 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.

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.

To study the toxic effect of chronic exposure to 3-chloro-1,2-propanediol (3-MCPD) at low doses, a metabonomics approach based on ultrahigh-performance liquid chromatography and quadruple time-of-flight mass spectrometry (UPLC–Q-TOF-MS) was performed. Two different doses of 3-MCPD (1.1 and 5.5 mg/kg bw/d) were administered to Wistar rats for 120 days (1.1 mg/kg bw/d: lowest observed adverse effect level [LOAEL]). The metabolite profiles and biochemical parameters were obtained at five time points after treatment. For the 3-MCPD-treated groups, a significant change in urinary N-acetyl-β- d -glucosaminidase and β- d -galactosidase was detected on day 90, while some biomarkers based on the metabonomics, such as N-acetylneuraminic acid, N-acetyl- l -tyrosine, and gulonic acid, were detected on day 30. These results suggest that these biomarkers changed more sensitively and earlier than conventional biochemical parameters and were thus considered early and sensitive biomarkers of exposure to 3-MCPD; these biomarkers provide more information on toxicity than conventional biochemical parameters. These results might be helpful to investigate the toxic mechanisms of 3-MCPD and provide a scientific basis for assessing the effect of chronic exposure to low-dose 3-MCPD on human health.