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N-acetylcysteine (NAC) possesses a strong capability to ameliorate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice, but the underlying mechanism is still unknown. Our study aimed to clarify the involvement of long non-coding RNA (lncRNA) in the beneficial effects of NAC on HFD-induced NAFLD. C57BL/6J mice were fed a normal-fat diet (10 % fat), a HFD (45 % fat) or a HFD plus NAC (2 g/l). After 14-week of intervention, NAC rescued the deleterious alterations induced by HFD, including the changes in body and liver weights, hepatic TAG, plasma alanine aminotransferase, plasma aspartate transaminase and liver histomorphology (haematoxylin and eosin and Oil red O staining). Through whole-transcriptome sequencing, 52 167 (50 758 known and 1409 novel) hepatic lncRNA were detected. Our cross-comparison data revealed the expression of 175 lncRNA was changed by HFD but reversed by NAC. Five of those lncRNA, lncRNA-NONMMUT148902·1 (NO_902·1), lncRNA-XR_001781798·1 (XR_798·1), lncRNA-NONMMUT141720·1 (NO_720·1), lncRNA-XR_869907·1 (XR_907·1), and lncRNA-ENSMUST00000132181 (EN_181), were selected based on an absolute log2 fold change value of greater than 4, P-value < 0·01 and P-adjusted value < 0·01. Further qRT-PCR analysis showed the levels of lncRNA-NO_902·1, lncRNA-XR_798·1, and lncRNA-EN_181 were decreased by HFD but restored by NAC, consistent with the RNA sequencing. Finally, we constructed a ceRNA network containing lncRNA-EN_181, 3 miRNA, and 13 mRNA, which was associated with the NAC-ameliorated NAFLD. Overall, lncRNA-EN_181 might be a potential target in NAC-ameliorated NAFLD. This finding enhanced our understanding of the biological mechanisms underlying the beneficial role of NAC.
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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.
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Dieta , Flavonoides/administración & dosificación , Magnesio , Síndrome Metabólico , Adulto , Anciano , China/epidemiología , Humanos , Quempferoles , Luteolina , Magnesio/administración & dosificación , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Obesidad , Obesidad Abdominal/epidemiología , Polifenoles , Estudios Prospectivos , Quercetina , Factores de Riesgo , Adulto JovenRESUMEN
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.
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COVID-19/epidemiología , Inocuidad de los Alimentos , Conocimientos, Actitudes y Práctica en Salud , Estado Nutricional , Adolescente , Adulto , China/epidemiología , Escolaridad , Epidemias , Conducta Alimentaria , Femenino , Frutas , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Bocadillos , Encuestas y Cuestionarios , Verduras , Adulto JovenRESUMEN
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.
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Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/farmacología , Animales , Peso Corporal/efectos de los fármacos , Resistencia a la Insulina , Interleucina-6/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Ácido Palmítico/farmacología , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Ácidos Esteáricos/farmacología , Factor de Necrosis Tumoral alfa/sangreRESUMEN
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.
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Calcifediol , Deficiencia de Vitamina D , Niño , China/epidemiología , Estudios Transversales , Humanos , Prevalencia , Estaciones del Año , Vitamina D/análogos & derivados , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/prevención & controlRESUMEN
OBJECTIVE: To explore the relationship between spicy food intake and overweight or obesity in the population, and provide theoretical basis for dietary prevention of obesity. METHODS: 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. RESULTS: 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, P<0.001) in males and 33%(OR=1.329, 95%CI 1.294-1.364, P<0.001) 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(P<0.001). CONCLUSION: 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.
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Obesidad , Sobrepeso , Adulto , Anciano , Índice de Masa Corporal , Peso Corporal , China , Estudios Transversales , Dieta , Conducta Alimentaria , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.
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Señalización del Calcio/genética , Enfermedades Cardiovasculares/metabolismo , Canales Catiónicos TRPC/genética , Factor de Necrosis Tumoral alfa/genética , Molécula 1 de Adhesión Celular Vascular/genética , Calcio/metabolismo , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/patología , Adhesión Celular/genética , Células Endoteliales de la Vena Umbilical Humana , Humanos , Sistema de Señalización de MAP Quinasas , Monocitos/metabolismo , Monocitos/patología , FN-kappa B/genética , FN-kappa B/metabolismo , Canales Catiónicos TRPC/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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 < 0.01 and <0.01 for type 2 diabetes, and ptrend < 0.01 and =0.02 for HbAlc, respectively, in each cohort) independent of TAC, adjusted for age, sex, BMI, tobacco use, alcohol consumption, physical activity, diabetes inheritance, total energy, carbohydrate, total fatty acids, fibre, calcium, Mg, hypertension, hyperlipidaemia, and impaired glucose tolerance or FBG (all at baseline). Their inverse association was stronger in the presence of diets with high, compared with low, TAC. In RCS, intakes of >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. CONCLUSIONS/INTERPRETATION: 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.
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Diabetes Mellitus Tipo 2/fisiopatología , Dieta , Manganeso/administración & dosificación , Adulto , Anciano , Antropometría , Antioxidantes/metabolismo , Glucemia , Índice de Masa Corporal , China , Diabetes Mellitus Tipo 2/prevención & control , Femenino , Estudios de Seguimiento , Intolerancia a la Glucosa/fisiopatología , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Dinámicas no Lineales , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Análisis de Regresión , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: 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. SUBJECTS/METHODS: 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. RESULTS: In combined data of the two cohorts, the cross-lagged path coefficient (ß1 = 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 (ß2 = 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 ß1 and ß2) 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 (ß1) 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 ß1s 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. CONCLUSIONS: 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.
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Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/fisiopatología , Hiperuricemia/complicaciones , Hiperuricemia/fisiopatología , Obesidad/complicaciones , Obesidad/fisiopatología , Ácido Úrico/sangre , Adulto , Anciano , Índice de Masa Corporal , China/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Hiperuricemia/epidemiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Factores de Riesgo , Circunferencia de la Cintura , Adulto JovenRESUMEN
AIMS/HYPOTHESIS: Serum stearic acid (C18:0) is elevated in individuals with hyperlipidaemia and type 2 diabetes. However, the lipotoxicity induced by increased stearic acid in beta cells has not been well described. This study aimed to examine the adverse effects of stearic acid on beta cells and the potential mechanisms through which these are mediated. METHODS: Three groups of C57BL/6 mice were fed a normal diet or a high-stearic-acid/high-palmitic-acid diet for 24 weeks, respectively. The microRNA (miR) profiles of islets were determined by microarray screening. Islet injury was detected with co-staining using the TUNEL assay and insulin labelling. A lentiviral vector expressing anti-miRNA-34a-5p oligonucleotide (AMO-34a-5p) was injected into mice via an intraductal pancreatic route. RESULTS: In both mouse islets and cultured rat insulinoma INS-1 cells, stearic acid exhibited a stronger lipotoxic role than other fatty acids, owing to repression of B cell CLL/lymphoma 2 (BCL-2) and BCL-2-like 2 (BCL-W) by stearic acid stimulation of miR-34a-5p. The stearic-acid-induced lipotoxicity and reduction in insulin secretion were alleviated by AMO-34a-5p. Further investigations in INS-1 cells revealed that p53 was involved in stearic-acid-induced elevation of miR-34a-5p, owing in part to activation of protein kinase-like endoplasmic reticulum kinase (PERK). Conversely, silencing PERK alleviated stearic-acid-induced p53, miR-34a-5p and lipotoxicity. CONCLUSIONS/INTERPRETATION: These findings provide new insight for understanding the molecular mechanisms underlying not only the deleterious impact of stearic-acid-induced lipotoxicity but also apoptosis in beta cells and progression to type 2 diabetes.
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Hiperlipidemias/metabolismo , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , MicroARNs/metabolismo , Ácidos Esteáricos/farmacología , Animales , Línea Celular , Insulina/metabolismo , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Ácidos Palmíticos/farmacología , Ratas , eIF-2 Quinasa/genética , eIF-2 Quinasa/metabolismoRESUMEN
BACKGROUND: Results of longitudinal researches regarding the temporal relationship between dyslipidemia and insulin resistance (IR) are inconsistent. This study assessed temporal relationships of blood lipids with IR and determined whether there are any mediating effects existed in these temporal relationships. METHODS: This study examined a longitudinal cohort of 3325 subjects aged 20-74 years from China with an average of 4.2 years follow-up. Measurements of fasting blood lipids, as well as fasting and 2-h serum glucose and insulin, were obtained at two time points. The Gutt index and HOMA-IR were calculated as indicators of peripheral IR and hepatic IR. A cross-lagged path analysis was performed to examine the temporal relationships between blood lipids and IR. A mediation analysis was used to examine mediating effect. RESULTS: After adjusting for covariates, the cross-lagged path coefficients from baseline TG and HDL-C to follow-up Gutt index were significantly greater than those from baseline Gutt index to follow-up TG and HDL-C (ß1 = -0.131 vs ß2 = -0.047, P < 0.001 for TG; ß1 = 0.134 vs ß2 = 0.023, P < 0.001 for HDL-C). The path coefficients from baseline TG and HDL-C to follow-up 2-h insulin were significantly greater than those from baseline 2-h insulin to follow-up TG and HDL-C (ß1 = 0.125 vs ß2 = 0.040, P < 0.001 for TG; ß1 = -0.112 vs ß2 = -0.026, P < 0.001 for HDL-C). 2-h insulin partially mediated the effect of TG/HDL-C on Gutt index with a 59.3% mediating effect for TG and 61.0% for HDL-C. CONCLUSIONS: These findings provide strong evidence that dyslipidemia probably precede peripheral IR and that 2-h insulin partially mediates this unidirectional temporal relationship.
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Glucemia/metabolismo , HDL-Colesterol/sangre , Dislipidemias/sangre , Resistencia a la Insulina , Insulina/sangre , Triglicéridos/sangre , Adulto , Anciano , Biomarcadores/sangre , China , Progresión de la Enfermedad , Dislipidemias/diagnóstico , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Estudios Prospectivos , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: Vinegar has been reported to lower blood pressure, but its mechanism is unclear. This study explored whether vinegar plays antihypertensive effect by activating AMP-activated protein kinase (AMPK) pathway. METHODS: Male spontaneously hypertensive rats (SHRs) were assigned to vinegar, acetic acid, nifedipine, nifedipine + vinegar, or distilled water by oral gavage for 8 weeks. Blood and aortas were analyzed for biochemical indices and protein expression levels. Sv40-transformed aortic rat endothelia cell line (SVAREC) cells were treated with acetate at different doses for 24 h; protein expression levels were assessed. RESULTS: Vinegar and acetic acid decreased blood pressure in SHRs on weeks 6 and 8, and nifedipine + vinegar had a better effect on blood pressure control than vinegar or nifedipine alone. Vinegar and acetic acid could decrease serum renin and angiotensin-converting enzyme (ACE) activities, angiotensin II and aldosterone concentrations in SHRs. Vinegar and acetic acid also increased AMP/ATP ratios and expression levels of pAMPK, PPARγ coactivator-1α (PGC-1α), and PPARγ while inhibited angiotensin II type 1 receptor (AT1R) expression in SHRs. The changes in these protein expressions were also found in SVAREC cells treated with 200 or 400 µmol/L acetate. In the presence of AMPK inhibitor or PGC-1α small interfering RNA, the effects of acetate on their downstream protein expression in SVAREC cells were abolished, respectively. CONCLUSION: Vinegar activates AMPK by increasing AMP/ATP ratios, thereby increases PGC-1α and PPARγ expressions, and inhibits AT1R expression in SHRs. Acetic acid is responsible for the antihypertensive effects of vinegar. There is a joint effect between vinegar and nifedipine in blood pressure control.
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Proteínas Quinasas Activadas por AMP/metabolismo , Ácido Acético/farmacología , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Regulación hacia Abajo , Receptor de Angiotensina Tipo 1/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Animales , Bloqueadores de los Canales de Calcio/farmacología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Silenciador del Gen , Masculino , Nifedipino/farmacología , PPAR gamma/genética , PPAR gamma/metabolismo , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/genética , Renina/sangre , Transducción de Señal , Acetato de Sodio/farmacologíaRESUMEN
OBJECTIVE: To ingvestigate effects of long-term high-fat diet on the energy and lipid metabolism. METHODS: 20 SPF male C57BL/6 mice were randomly divided into a control group fed a basic diet and a high-fat group fed a high-fat diet. Indirect calorimetry measurement was done to mearue total energy expenditure and metabolism in the mice at the 12th week. Multi-row quantitative CT was applied to detect body fat content and distribution in the mice. At the end of the experiment the mice were killed, and blood and liver were collected to detect the bio6hemical and histopathological indicators. RESULTS: In comparison with the control group, the mice fed high-fat diet increased energy intake, body and visceral fat content and levels of fatty acid oxidation were significantlyincreased (P <0. 05). Fasting blood glucose, blood lipid, insulin and fatty acid content in liver and serum were significantly higher than those in the control group(P <0. 05). Pathology examinations showed hepatocytes steatosis, mitochondria and other organelles structural damage in the high-fat mice. CONCLUSION: Long-term high-fat diet can lead to excessive energy intake, lipid dysmetabolism, abdominal obesity, hyperlipidemia, fatty liver and insulin resistance.
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Dieta Alta en Grasa/efectos adversos , Ingestión de Energía , Metabolismo Energético , Metabolismo de los Lípidos , Tejido Adiposo , Animales , Ácidos Grasos , Hígado Graso , Hiperlipidemias , Insulina , Resistencia a la Insulina , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones ObesosRESUMEN
The rapidly emerging prevalence of type 2 diabetes mellitus (T2DM) and its associated complications have formed an increasingly serious threat to human life and health. Therefore, there is an urgent requirement to investigate the pathogenesis of T2DM and its complications, which will be conducive to discovering effective drugs for prevention and treatment. N6-methyladenosine (m6A) methylation is the most abundant and prevalent epigenetic modification of mRNA in mammals. m6A methylation is a dynamically reversible epigenetic transcriptome modification process that is jointly regulated by methyltransferases, demethylases and methylated reading proteins, which control the fate of target mRNAs through influencing splicing, translation and decay. Recent studies have revealed that m6A methylation plays an important role in ß cellular function, insulin sensitivity and glycolipid metabolism. In this review, we summarized the current roles of m6A methylation in T2DM and T2DM-related complications such as diabetes nephropathy (DN), diabetes cardiovascular disease (DCD) and diabetes retinopathy (DR). Additionally, we sought the potential mechanism of m6A in T2DM and related complications, which may provide a rationale and strategy for potential therapeutic targeting of T2DM and its complications.
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OBJECTIVES: This study aimed to explore the temporal relationship between blood glucose, lipids and body mass index (BMI), and their impacts on atherosclerosis (AS). DESIGN: A prospective cohort study was designed. SETTING AND PARTICIPANTS: A total of 2659 subjects from Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases, and aged from 20 to 74 years were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Body weight, height, fasting blood glucose (FBG) and 2-hour postprandial glucose (2-h PG), blood lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) were measured at baseline and follow-up. Brachial ankle pulse wave velocity (baPWV) was examined at follow-up as a marker of AS risk. Logistic regression analysis, cross-lagged path analysis and mediation analysis were performed to explore the temporal relationships between blood glucose, lipids and BMI, and their impacts on AS risk. RESULTS: Logistic regression analysis indicated that increased FBG, 2-h PG, TC, TG, LDL-c and BMI were positively associated with AS risk, while increased HDL-c was negatively associated with AS risk. The path coefficients from baseline blood parameters to the follow-up BMI were significantly greater than those from baseline BMI to the follow-up blood parameters. Mediation analysis suggested that increased FBG, 2-h PG, TC, TG and LDL-c could increase AS risk via increasing BMI, the effect intensity from strong to weak was LDL-c>TC>TG>FBG>2 h PG, while increased HDL-c could decrease AS risk via decreasing BMI. CONCLUSIONS: Changes in blood glucose and lipids could cause change in BMI, which mediated the impacts of blood glucose and lipids on AS risk. These results highlight the importance and provide support for the early and comprehensive strategies of AS prevention and control.
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Aterosclerosis , Glucemia , Índice de Masa Corporal , Lípidos , Humanos , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Glucemia/metabolismo , Glucemia/análisis , Femenino , Aterosclerosis/sangre , Aterosclerosis/etiología , Adulto , Lípidos/sangre , Anciano , Factores de Riesgo , Análisis de la Onda del Pulso , Adulto Joven , China/epidemiología , Índice Tobillo Braquial , Triglicéridos/sangre , Modelos LogísticosRESUMEN
BACKGROUND: Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. METHODS: The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. RESULTS: Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson correlation, r = 0.53, P = 0.0001) and citrate (Pearson correlation, r = -0.43, P = 0.001), were further confirmed in 70 women. CONCLUSIONS: To our knowledge, this is the first report of reliable biomarkers of calcium deficiency, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of calcium deficiency. The correlations between calcium intake and two of the biomarkers provide a rationale or potential for further assessment and elucidation of the metabolic responses of calcium deficiency in humans.
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Biomarcadores/orina , Calcio/deficiencia , Metaboloma , Orina/química , Animales , Cromatografía Liquida , Femenino , Humanos , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Ratas , Ratas Wistar , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
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.
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Sulfato de Deshidroepiandrosterona/sangre , Diabetes Mellitus Tipo 2/sangre , Ayuno/sangre , Lípidos/sangre , Metabolómica , Cromatografía Líquida de Alta Presión/métodos , Sulfato de Deshidroepiandrosterona/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Metabolismo de los Lípidos , Masculino , Metaboloma , Metabolómica/métodos , Persona de Mediana Edad , Espectrometría de Masas en Tándem/métodosRESUMEN
Previously, we showed that mice fed white button mushrooms (WBM) had enhanced immune functions known to help the body's antiviral defence. In the present study, we tested whether WBM conferred protection against viral infection. Young (4-month-old) and old (22-month-old) C57BL/6 mice were fed a diet containing 0, 2 or 10 % WBM powder for 8 weeks. Mice were then infected with influenza Puerto Rico/8/34 (H1N1), and killed at day 0 (uninfected), 2, 5 or 7 post-infection. The primary outcomes of the study were viral titre and body weight. Secondary outcomes were natural killer (NK) cell activity, lymphocyte proliferation and cytokine production. The results showed that WBM did not affect viral titre, nor did it prevent infection-induced weight loss. WBM supplementation was found to enhance NK cell activity in old mice and to increase interferon (IFN)-γ production in young and old mice under naive (uninfected) conditions, but it had no such effect after infection. The lack of a mushroom supplementation effect on NK activity and concanavalin A-stimulated IFN-γ production after infection may explain the immune system's failure to reduce viral load and weight loss in mice after influenza infection. WBM supplementation, however, did induce changes in other aspects of the immune response: it significantly increased the production of T-helper type 2 cytokines IL-4 and IL-10 in uninfected mice and pro-inflammatory cytokines IL-1ß and TNF-α in infected mice. These mushroom-induced systemic changes, however, were not adequate to confer a protective effect against influenza infection.
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Agaricales , Dieta , Resistencia a la Enfermedad/inmunología , Infecciones por Orthomyxoviridae/inmunología , Animales , Concanavalina A/farmacología , Alimentos en Conserva , Subtipo H1N1 del Virus de la Influenza A , Interferones/biosíntesis , Células Asesinas Naturales/inmunología , Pulmón/virología , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Infecciones por Orthomyxoviridae/complicaciones , Infecciones por Orthomyxoviridae/prevención & control , Carga Viral , Pérdida de PesoRESUMEN
OBJECTIVE: To investigate the changes in blood lipids and fatty acids profile of mice after different oil loading, and explore the effects of different dietary fatty acids on postprandial blood lipids and fatty acid profile. METHODS: Ninety-six C57BL/6 mice were randomly divided into 2 groups by weight ,maize germ oil group and lard oil group. The mice were given maize germ oil or lard oil by gavage at a dose of 1 ml/100 mg BW, respectively, after over-night fasting. At 0, 30, 60, 120, 180 and 240 min after oil loading, 8 mice were selected randomly from both groups, respectively, and blood was collected via orbital bleeding for postprandial blood lipids and fatty acid profile analysis. RESULTS: The serum triglycerides and total free fatty acids levels in mice loaded with lard oil were significantly higher than those in mice loaded with maize germ oil, respectively, at 120, 180, 240 min. The serum saturated fatty acids and monounsaturated fatty acids in mice loaded with lard oil were significantly higher, whereas serum polyunsaturated fatty acids were significantly lower than those in mice loaded with maize germ oil at 60, 120, 180 and 240 min (P < 0.05). Serum palmitic oil and oleic oil in mice loaded with lard oil were higher, whereas linoleic oil and arachidonic acid were lower than those in mice loaded with maize germ oil at 60, 120, 180 and 240 min (P < 0.05). CONCLUSION: Compared with maize germ oil, lard oil leads to higher postprandial serum triglycerides and saturated fatty acids levels, that may increase the risk of cardiovascular diseases.
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Aceite de Maíz/administración & dosificación , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/química , Lípidos/sangre , Alimentación Animal , Animales , Ácidos Grasos/sangre , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
The effects of a natural soda water (Shi Han Quan, SHQ) on hyperlipidemia and the changes of urine metabolic profiling by metabolomics techniques were investigate. Thirty six Wistar rats weighing 160-200 g were divided into control group, hyperlipidemia (HL) group, and hyperlipidemia + SHQ water (SHQ) group. The metabolites in urine were determined using ultra high performance liquid chromatography-triple-time of flight-mass spectrometry (UPLC/Triple-TOF MS). At the end of 1 month and 3 months, the total glyceride (TG) level was significantly lower in SHQ group compared to HL group. There was no significantly difference in total cholesterol (TC) levels in HL group compared with SHQ group. The results showed that dinking SHQ water can improve the TG, but with no effects on TC. After drinking SHQ water for 3 months, the rats in different groups could be classified into different clusters according to the metabolites in urine. Total 15 important metabolites were found and correlated with disturbance of amino acid, phospholipid, fatty acid and vitamin metabolism, which suggested the changes of metabolism in the body and possible mechanism by which SHQ improved the TG. These findings provide a new insight for the prevention and control of hyperlipidemia.