RESUMEN
Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway.
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Fibrosis , Ratones Endogámicos C57BL , Infarto del Miocardio , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Ratones , Masculino , Proteínas Señalizadoras YAP/metabolismo , Fibroblastos/metabolismo , Citidina/análogos & derivados , Citidina/farmacología , Ratones Noqueados , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Acetiltransferasa E N-Terminal/metabolismo , Vía de Señalización Hippo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Células Cultivadas , Transducción de Señal , Acetiltransferasas N-Terminal/metabolismo , Miocardio/patología , Miocardio/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
Exploring the effects of ant nests on soil CH4 emissions in the secondary tropical forests is of great scientific significance to understand the contribution of soil faunal activities to greenhouse gas emissions. With static chamber-gas chromatography method, we measured the dry-wet seasonal dynamics of CH4 emissions from ant nests and control soils in the secondary forest of Syzygium oblatum communities in Xishuangbanna. We also examined the linkages of ant-mediated changes in functional microbial diversity and soil physicochemical properties with CH4 emissions. The results showed that: 1) Ant nests significantly accelerated soil CH4 emissions, with average CH4 emissions in the ant nests being 2.6-fold of that in the control soils. 2) The CH4 emissions had significant dry-wet seasonal variations, which was a carbon sink in the dry seasons (from -0.29±0.03 to -0.53±0.02 µg·m-2·h-1) and a carbon source in the wet seasons (from 0.098±0.02 to 0.041±0.009 µg·m-2·h-1). The CH4 emissions were significantly higher in ant nests than in control soils. The CH4 emissions from the ant nests had smaller dry-wet seasonal variation (from -0.38±0.01 to 0.12±0.02 µg·m-2·h-1) than those in the control soils (from -0.65±0.04 to 0.058±0.006 µg·m-2·h-1). 3) Ant nests significantly increased the values (6.2%-37.8%) of soil methanogen diversity (i.e., Ace and Shannon indices), temperature and humidity, carbon pools (i.e., total, easily oxidizable, and microbial carbon), and nitrogen pools (i.e., total, hydrolyzed, ammonium, and microbial biomass nitrogen), but decreased the diversity (i.e., Ace and Chao1 indices) of methane-oxidizing bacteria by 21.9%-23.8%. 4) Results of the structural equation modeling showed that CH4 emissions were promoted by soil methanogen diversity, temperature and humidity, and C and N pools, but inhibited by soil methane-oxidizing bacterial diversity. The explained extents of soil temperature, humidity, carbon pool, nitrogen pool, methanogen diversity, and methane-oxidizing bacterial diversity for the CH4 emission changes were 6.9%, 21.6%, 18.4%, 15.2%, 14.0%, and 10.8%, respectively. Therefore, ant nests regulated soil CH4 emission dynamics through altering soil functional bacterial diversities, micro-habitat, and carbon and nitrogen pools in the secondary tropical forests.
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Hormigas , Bosques , Metano , Suelo , Clima Tropical , Metano/análisis , Metano/metabolismo , Animales , Suelo/química , China , Microbiología del Suelo , Estaciones del AñoRESUMEN
SCOPE: Endocannabinoid signaling regulates energy homeostasis, and is tightly associated with nonalcoholic fatty liver disease (NAFLD). The study previously finds that supplementation of docosahexaenoic acid (DHA) has superior function to ameliorate NAFLD compared with eicosapentaenoic acid (EPA), however, the underlying mechanism remains elusive. The present study aims to investigate whether DHA intervention alleviates NAFLD via endocannabinoid system. METHODS AND RESULTS: In a case-control study, the serum endocannabinoid ligands in 60 NAFLD and 60 healthy subjects are measured. Meanwhile, NAFLD model is established in mice fed a high-fat and -cholesterol diet (HFD) for 9 weeks. DHA or EPA is administrated for additional 9 weeks. Serum primary endocannabinoid ligands, namely anandamide (AEA) and 2-arachidoniylglycerol (2-AG), are significantly higher in individuals with NAFLD compared with healthy controls. NAFLD model shows that serum 2-AG concentrations and adipocyte cannabinoid receptor 1 expression levels are significantly lower in DHA group compared with HFD group. Lipidomic and targeted ceramide analyses further confirm that endocannabinoid signaling inhibition has exerted deletion of hepatic C16:0-ceramide contents, resulting in down-regulation of de novo fatty acid synthesis and up-regulation of fatty acid ß-oxidation related protein expression levels. CONCLUSIONS: This work elucidates that DHA has improved NAFLD by suppressing endocannabinoid system.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/metabolismo , Endocannabinoides/metabolismo , Estudios de Casos y Controles , Hígado/metabolismo , Ácido Eicosapentaenoico/farmacología , Ceramidas/metabolismo , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
We previously reported that fish oil plus vitamin D3 (FO + D) could ameliorate nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether the beneficial effects of FO + D on NAFLD are associated with gut microbiota and fecal metabolites. In this study, we investigated the effects of dietary supplementation of FO + D on gut microbiota and fecal metabolites and their correlation with NAFLD risk factors. Methods: A total of 61 subjects were randomly divided into three groups: FO + D group (2.34 g day-1 of eicosatetraenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3), FO group (2.34 g day-1 of EPA + DHA), and corn oil (CO) group (1.70 g d-1 linoleic acid). Blood and fecal samples were collected at the baseline and day 90. Gut microbiota were analyzed through 16S rRNA PCR analysis, and fecal co-metabolites were determined via untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results: The relative abundance of Eubacterium (p = 0.03) and Lactobacillus (p = 0.05) increased, whereas that of Streptococcus (p = 0.02) and Dialister (p = 0.04) decreased in the FO + D group compared with the CO group. Besides, changes in tetracosahexaenoic acid (THA, C24:6 n-3) (p = 0.03) levels were significantly enhanced, whereas 8,9-DiHETrE levels (p < 0.05) were reduced in the FO + D group compared with the CO group. The changes in 1,25-dihydroxyvitamin D3 levels in the fecal samples were inversely associated with insulin resistance, which was determined using the homeostatic model assessment model (HOMA-IR, r = -0.29, p = 0.02), and changes in 8,9-DiHETrE levels were positively associated with adiponectin levels (r = -0.43, p < 0.05). Conclusion: The present results indicate that the beneficial effects of FO + D on NAFLD may be partially attributed to the impact on gut microbiota and fecal metabolites.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Humanos , Aceites de Pescado/farmacología , Colecalciferol/farmacología , ARN Ribosómico 16S , Vitamina D/farmacología , Suplementos DietéticosRESUMEN
n-3 polyunsaturated fatty acids (PUFA) have shown to exert beneficial effects in the treatment of nonalcoholic fatty liver disease (NAFLD). Supplements of n-3 PUFA occur in either phospholipid or triacylglycerol form. The present study aimed to compare whether the different n-3 PUFA of marine-origin, namely krill oil, DHA/EPA-phospholipid (PL), and EPA/DHA-triacylglycerol (TAG) forms had differential abilities to ameliorate NAFLD. The NAFLD model was established in mice fed a high-fat and high-cholesterol diet (HFD). The mice showed evidence of weight gain, dyslipidemia, insulin resistance and hepatic steatosis after 9 weeks of HFD, while the three forms of the n-3 PUFA reduced hepatic TAG accumulation, fatty liver and improved insulin instance, and hepatic biomarkers after 9 weeks of intervention. Of these, krill oil intervention significantly reduced adipocyte hypertrophy and hepatic steatosis in comparison with DHA/EPA-PL and EPA/DHA-TAG groups. Importantly, only krill oil intervention significantly reduced serum alanine transaminase, aspartate transaminase concentrations and low-density lipoprotein-cholesterol, compared with the HFD group. Supplemental n-3 PUFA lowered circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) concentrations, compared with the HFD group, which was associated with down-regulating CB1 and upregulating adiponectin expressions in adipose tissue. Besides, targeted lipidomic analyses indicated that the increased adiponectin levels were accompanied by reductions in hepatic ceramide levels. The reduced ceramide levels were associated with inhibiting lipid synthesis and increasing fatty acid ß-oxidation, finally inhibiting TAG accumulation in the liver. Through mediating CB1/adiponectin/ceramide pathway, the present study suggested that administration of krill oil had superior health effects in the therapy of NAFLD in comparison with DHA/EPA-PL and EPA/DHA-TAG.
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Ácidos Grasos Omega-3 , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Grasos Omega-3/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fosfolípidos/metabolismo , Adiponectina/metabolismo , Triglicéridos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Hígado/metabolismo , Ácidos Grasos Insaturados/metabolismo , Colesterol/metabolismo , Receptores de Cannabinoides/metabolismo , Ácidos Grasos/metabolismoRESUMEN
The aim of the present study was to investigate the relationship between the changes of serum lipid metabolites and the risk factors of non-alcoholic fatty liver disease (NAFLD) after fish oil (FO) or fish oil plus vitamin D (FO + D) intervention in Chinese NAFLD subjects. Seventy-four NAFLD subjects, aged 55.2 ± 15.9 years, were randomized to consume FO + D (n = 23), FO (n = 27) or corn oil (CO, n = 24) capsules for a 3-month intervention. Serum lipid-related metabolites were measured with ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomics approach together with multivariate data analysis. The differential metabolites were screened and identified with variable importance in projection (VIP) scores based on orthogonal partial least squares discriminant analysis models. Serum phosphatidylcholine (PC) (16:1/22:6) levels had the highest and second highest VIP scores following FO + D and FO interventions, respectively. Serum PC (16:1/22:6) levels were negatively correlated with circulating alanine transaminase (ALT) (r = -0.268, p = 0.021), triacylglycerol (TAG) (r = -0.236, p = 0.042), interleukin (IL)-1ß (r = -0.401, p < 0.001) and tumor necrosis factor (TNF)-α (r = -0.322, p = 0.005) concentrations, and were positively correlated with high-density lipoprotein cholesterol (HDL-C) (r = 0.272, p = 0.019) concentrations. The present study was the first to report that serum PC (16:1/22:6) levels were highly correlated with ALT, TAG, HDL-C, IL-1ß and TNF-α concentrations, indicating that PC (16:1/22:6) might ameliorate lipid metabolism and inflammation in NAFLD subjects.
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Aceites de Pescado , Enfermedad del Hígado Graso no Alcohólico , Humanos , Aceites de Pescado/química , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Colecalciferol , Fosfatidilcolinas , Biomarcadores , Triglicéridos , HDL-Colesterol , Factor de Necrosis Tumoral alfa , Alanina Transaminasa , ChinaRESUMEN
OBJECTIVES: The fibroblast growth factor 21 (FGF21)-adiponectin axis participates in energy hemostasis and obesity-related syndrome. The present study aimed to investigate whether concentrated fish oil (FO) intervention could alleviate non-alcoholic fatty liver disease (NAFLD) via the regulation of the FGF21-adiponectin axis. METHODS: In a randomized controlled trial, 61 patients with NAFLD, age 55.9 ± 15.6 y, were randomly divided into two groups: FO (3 g/d; n = 30) and corn oil (CO; 3 g/d; n = 31), which served as the control group. RESULTS: After a 3-mo intervention, there were significant net reductions in serum alanine transaminase (-5.4 ± 14.5 U/L vs. -0.25 ± 4.70 U/L; P = 0.001) and triacylglycerol (-0.70 ± 1.10 mmol/L vs. 0.11 ± 1.04 mmol/L; P = 0.018) levels in the FO group compared with the CO group. Furthermore, the mean changes of FGF21 levels (-16.3 ± 20.1 pg/mL vs. 7.2 ± 32.9 pg/mL; P = 0.002) were significantly decreased, but adiponectin levels (1.14 ± 1.53 µg/mL vs. -0.42 ± 2.04 pg/mL; P = 0.011) were significantly increased in the FO group compared with the CO group. In the animal study, the mice fed the high-fat diet demonstrated characteristics of NAFLD. The administration of FO significantly improved high-fat diet-induced hepatic steatosis, insulin resistance, and inflammation compared with the high-fat control group. In addition, FO improved the sensitivity of FGF21, and stimulated the expression levels of adiponectin in the liver. CONCLUSIONS: The present study suggested that FO could potentially ameliorate NAFLD through mediating the FGF21-adiponectin axis.
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Enfermedad del Hígado Graso no Alcohólico , Adiponectina , Anciano , Animales , Dieta Alta en Grasa , Factores de Crecimiento de Fibroblastos , Aceites de Pescado/farmacología , Humanos , Hígado/metabolismo , Ratones , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: The present study aimed to investigate the hypothesis that dietary amino acid intakes are associated with the risk of sarcopenia through a community-based observational study. METHODS AND STUDY DESIGN: A total of 1,140 participants (72.7±6.3 y) were recruited from an annual health check-up program in Qingdao, China. Skeletal muscle mass, muscle mass functions and biochemical parameters were measured by standard methods. Dietary intake was assessed by 3-day, 24-hour food records. The odds ratios (ORs) and 95% confidence intervals (CIs) of sarcopenic risk across quartiles of amino acid intakes were calculated using a multivariable- adjusted logistic regression model. Generalized linear models were used to assess the associations between dietary amino acid intakes and muscle mass functions. RESULTS: The prevalence of sarcopenia was 4.1%. Compared with the lowest category intake, the highest category of branched chain amino acids (BCAAs) (OR=0.11; 95% CI: 0.01, 0.90; p for trend=0.119), isoleucine (OR=0.11; 95% CI: 0.01, 0.89; p for trend=0.122) and tryptophan (OR=0.10; 95% CI: 0.01, 0.87; p for trend=0.176) was negatively correlated with sarcopenic risk with adjustment for potential confounding factors. Generalized linear model analysis showed that gait speed was positively correlated with dietary intakes of lysine, threonine, leucine, valine, tryptophan, BCAAs and aromatic amino acids (p<0.05). CONCLUSIONS: Higher intakes of BCAAs were associated with a lower risk of sarcopenia, which might beneficially protect against sarcopenia and improve physical function of the elderly.
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Sarcopenia , Anciano , Aminoácidos de Cadena Ramificada/metabolismo , Dieta , Humanos , Oportunidad Relativa , Factores de Riesgo , Sarcopenia/epidemiología , Sarcopenia/prevención & controlRESUMEN
PURPOSE: The present study aimed to investigate fish oil plus vitamin D3 (FO + D) supplementation on biomarkers of non-alcoholic fatty liver disease (NAFLD). METHODS: In a 3-month randomized controlled trial, 111 subjects with NAFLD, aged 56.0 ± 15.9 y, were randomized into FO + D group (n = 37), fish oil group (FO, n = 37) or corn oil group (CO, n = 37). The subjects consumed the following capsules (3 g/day), which provided 2.34 g/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3 (FO + D group), or 2.34 g/day of EPA + DHA (FO group), or 1.70 g/d linoleic acid (CO group). RESULTS: Using multivariable-adjusted general linear model, there were significant net reductions in serum alanine aminotransferase (ALT), and triacylglycerol (TAG) and TNF-α levels in the FO + D and FO groups, compared with the control group (P < 0.05). The supplemental FO + D also showed significant reductions in insulin (- 1.58 ± 2.00 mU/L vs. - 0.63 ± 1.55 mU/L, P = 0.050) and IL-1ß (- 6.92 ± 7.29 ng/L vs. 1.06 ± 5.83 ng/L, P < 0.001) in comparison with control group. Although there were no significant differences between FO + D and FO groups regarding biochemical parameters, supplemental FO + D showed decreases in ALT (from 26.2 ± 13.5 U/L to 21.4 ± 9.6 U/L, P = 0.007), aspartate aminotransferase (AST, from 22.5 ± 7.0 U/L to 20.2 ± 4.0 U/L, P = 0.029), HOMA-IR (from 3.69 ± 1.22 to 3.38 ± 1.10, P = 0.047), and TNF-α (from 0.43 ± 0.38 ng/L to 0.25 ± 0.42 ng/L, P < 0.001) levels following the intervention. CONCLUSION: The present study demonstrated that groups supplemented with FO + D and FO had similar beneficial effects on biomarkers of hepatocellular damage and plasma TAG levels in subjects with NAFLD, while in the FO + D group, there were some suggestive additional benefits compared with FO group on insulin levels and inflammation. TRIAL REGISTRATION: ChiCTR1900024866.
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Colecalciferol , Aceites de Pescado , Enfermedad del Hígado Graso no Alcohólico , Biomarcadores , Colecalciferol/administración & dosificación , Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Aceites de Pescado/administración & dosificación , Humanos , Insulina , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Triglicéridos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated optimizing retinal DHA using dietary ALA. Previous research identified 19% DHA in retinal phospholipids was associated with optimal retinal function in guinea pigs. Pregnant guinea pigs were fed dietary ALA from 2.8% to 17.3% of diet fatty acids, at a constant level of linoleic acid (LA) of 18% for the last one third of gestation and retinal DHA levels were assessed in 3-week-old offspring maintained on the same diets as their mothers. Retinal DHA increased in a linear fashion with the maximum on the diet with LA:ALA of 1:1. Feeding diets with LA:ALA of 1:1 during pregnancy and assessing retinal DHA in 3-week-old offspring was associated with optimized retinal DHA levels. We speculate that the current intakes of ALA in human diets, especially in relation to LA intakes, are inadequate to support high DHA levels in the retina.
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Dieta/métodos , Grasas de la Dieta/administración & dosificación , Ácidos Docosahexaenoicos/metabolismo , Retina/metabolismo , Ácido alfa-Linolénico/administración & dosificación , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Animales Recién Nacidos , Femenino , Cobayas , Ácido Linoleico/administración & dosificación , Fenómenos Fisiologicos Nutricionales Maternos , Fosfolípidos/metabolismo , EmbarazoRESUMEN
Epidemiological studies indicate that higher intakes of flavonoids are associated with reduced stroke risk, however, which subtypes play significant roles to protect against stroke remain unclear. A systematic literature search in PubMed and Web of Science databases was performed up to Oct. 2021. Flavonoids or their subtypes (flavanol, flavanone, flavone, flavan-3-ol, isoflavone, or anthocyanin) were paired with stoke as the search term. Multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) for the highest versus the lowest category were pooled by using a random-effects model. Dose-response analysis was implemented by using a restricted cubic spline regression model. Ten independent prospective cohort studies with 387,076 participants and 9,564 events were included. Higher intakes of flavanones were inversely associated with stroke risk (RR = 0.85; 95%CI: 0.78, 0.93). Dose-response analysis showed that 50 mg/day increment of flavanones was associated with 11% reduction in stroke risk (RR = 0.89; 95%CI: 0.84, 0.94). Flavan-3-ols was marginally inversely associated with stroke risk (RR = 0.92; 95%CI: 0.82, 1.02). Dose-response analysis showed that 200 mg/day increment of flavan-3-ols was associated with 14% reduction in stroke risk (RR = 0.86; 95%CI: 0.75, 0.98). The non-significant association was observed with respect to other flavonoid subclasses. This study demonstrated higher intakes of flavanones and flavan-3-ols were associated with a lower risk of stroke. Dietary intakes of lemon and citrus rich in flavanones and flavan-3-ols might have beneficial functions for the protection against stroke. The findings of these associations of the present study need to be confirmed in other regions and ethnic origins.
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Dieta , Accidente Cerebrovascular , Flavonoides , Humanos , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
Folate cannot prevent all neural tube defects (NTD), indicating that other pathogeneses still exist except for the folate deficiency. Maternal diabetes mellitus during pregnancy can increase the risk of offspring NTD. Our previous study showed that polyunsaturated fatty acids (PUFA) were lower in the placenta of human NTD cases than in healthy controls, and the supplementation of fish oil (rich in long-chain (LC) n-3 PUFA, mainly C20:5n-3 and C22:6n-3) had a better prevention effect against sodium valproate induced NTD than corn oil (rich in C18:2n-6) and flaxseed oil (rich in C18:3n-3). The aim of the present study was to investigate whether PUFA could prevent diabetes-induced NTD in mice. Streptozotocin (STZ)-induced diabetic pregnant mice were fed with a normal diet (DMC), a diet containing a low dose of fish oil (DMLn-3), a diet containing a high dose of fish oil (DMHn-3) or a diet rich in corn oil (DMn-6). Healthy pregnant mice were fed with a normal diet (HC). Compared with the DMC group, the rate of NTD was significantly lower in the DMHn-3 group (4.44% vs. 12.50%), but not in the DMLn-3 (11.11%) or DMn-6 group (12.03%). The NTD rate in the DMHn-3 group was comparable with that in the HC group (1.33%) (p = 0.246), and lower than that in the DMn-6 group (p = 0.052). The NTD rate in DMLn-3 and DMn-6 groups was significantly higher than that in the HC group. No significant difference was observed in NTD rate between DMLn-3 and DMHn-3 groups, and between DMLn-3 and DMn-6 groups. Compared with the HC group, the DMC group had a significantly lower C22:6n-3 in both serum and embryos. Fish oil supplementation ameliorated neuroepithelial cell apoptosis, and the apoptotic rate was comparable between DMHn-3 and HC groups. Although the apoptotic rate was significantly lower in the DMn-6 group than the DMC group, it was still much higher than that in the HC group. The proteins P53 and Bax in embryos were higher, while the proteins Bcl-2 and Pax3 were lower in the DMC group than in the HC group. The disturbance of Pax3, P53 and Bax induced by diabetes was abolished in DMLn-3, DMHn-3 and DMn-6 groups. Importantly, Bcl-2 in embryos was restored to the normal level only in the DMHn-3 group but not in the DMLn-3 or DMn-6 group. In conclusion, LC n-3 PUFA enriched fish oil has a protective effect against NTD in diabetes induced by STZ through improving neuroepithelial cell apoptosis, and the mechanism may be by increasing the anti-apoptosis protein Bcl-2 independently of Pax3 and P53.
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Diabetes Gestacional , Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Defectos del Tubo Neural/prevención & control , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas de Unión al ADN/metabolismo , Diabetes Mellitus Experimental , Dieta , Pérdida del Embrión , Embrión de Mamíferos/metabolismo , Ácidos Grasos/sangre , Ácidos Grasos Omega-6/administración & dosificación , Femenino , Aceites de Pescado , Ratones , Ratones Endogámicos ICR , Células Neuroepiteliales/fisiología , EmbarazoRESUMEN
BACKGROUND AND OBJECTIVES: As an endocrine organ, the mass of skeletal muscle is closely related to human health. The present study aimed to investigate the relationship between regional skeletal muscle and nonalcoholic fatty liver disease (NAFLD) in Chinese elders. METHODS AND STUDY DESIGN: A total of 1,328 participants (579 males and 749 females), aged 65 to 96 years were recruited between March to November 2020 in Qingdao, China. Of these, 400 cases and 400 healthy controls, matched by gender and age (±3 years), were included in the study. Skeletal muscle mass was measured by bioelectrical impedance analysis, and body weight was adopted to standardize skeletal muscle mass to obtain skeletal muscle mass indexes. RESULTS: Inverse associations were observed for trunk muscle mass index (TMI) (OR=0.42; 95% CI: 0.19, 0.93; p for trend=0.083) and leg skeletal muscle mass index (LMI) (OR=0.41; 95% CI: 0.18, 0.97; p for trend=0.012) with NAFLD risk after adjustment for age, body mass index, glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, dietary intakes of energy, carbohydrate, protein and fat, smoking, alcohol drinking, education and physical activity. Dose-response analysis indicated that per standard deviation increment of LMI was associated with 23% (95%CI: 0.63, 0.95) reduction of NAFLD risk. CONCLUSIONS: The present study demonstrates that higher TMI and LMI are associated with a lower NAFLD risk.
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Enfermedad del Hígado Graso no Alcohólico , Anciano , Índice de Masa Corporal , China/epidemiología , Ejercicio Físico , Femenino , Humanos , Masculino , Músculo Esquelético , Enfermedad del Hígado Graso no Alcohólico/epidemiologíaRESUMEN
BACKGROUND & AIMS: Previous randomized controlled trials (RCTs) have compared the effects of pure preparations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing metabolic syndrome (MetS) risk factors, but the results were inconsistent. The present study aimed to clarify whether EPA and DHA have differential effects on MetS features in humans. METHODS: A systematic literature search was conducted in CNKI, PubMed, Embase and Scopus updated to February 2021. The mean changes in the characteristics of MetS were calculated as weighted mean differences by using a random-effects model. Thirty-three RCTs were included. RESULTS: The results showed that both EPA and DHA were effective at lowering serum triglycerides (TG) levels. EPA supplementation decreased the serum levels of total cholesterol (TC) (WMD = -0.24 mmol/L; 95% CI, -0.43, -0.05 mmol/L), TG (WMD = -0.77 mmol/L; 95% CI, -1.54, -0.00 mmol/L) and low density lipoprotein-cholesterol (LDL-C) (WMD = -0.13 mmol/L; 95% CI, -0.25, -0.01 mmol/L), while DHA increased the serum levels of TC (WMD = 0.14 mmol/L; 95% CI, 0.03, 0.25 mmol/L), LDL-C (WMD = 0.26 mmol/L; 95% CI, 0.15, 0.38 mmol/L) and high density lipoprotein-cholesterol (HDL-C) (WMD = 0.07 mmol/L; 95% CI, 0.04, 0.09 mmol/L). Moreover, DHA increased the serum levels of insulin compared with EPA, especially in subgroups whose mean age was <60 years (0.43 mU/L; 95% CI: 0.04, 0.81 mU/L) and duration of DHA supplementation < 3 months (0.39 mU/L; 95% CI: 0.01, 0.77 mU/L). CONCLUSIONS: The present meta-analysis provides evidence that EPA and DHA have different effects on risk factors of MetS.
Asunto(s)
Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Ácido Eicosapentaenoico/administración & dosificación , Síndrome Metabólico/prevención & control , Adulto , Factores de Riesgo Cardiometabólico , Colesterol/sangre , HDL-Colesterol/sangre , HDL-Colesterol/efectos de los fármacos , LDL-Colesterol/sangre , LDL-Colesterol/efectos de los fármacos , Femenino , Humanos , Masculino , Síndrome Metabólico/etiología , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Triglicéridos/sangreRESUMEN
OBJECTIVE: The relationship between dietary nut intake and hyperuricemia risk remains unclear. The aim of this study was to investigate the relationship between different nut intake and hyperuricemia risk with a cross-sectional study. DESIGN: A semi-quantitative FFQ was adopted to collect dietary information. Biochemical and anthropometric parameters were measured by standard methods. Multivariate-adjusted logistic regression models were implemented to analyse the relationship between individual nut intake and hyperuricemia risk. SETTING: Qingdao University in Shandong Province, China. PARTICIPANTS: During 2018-2019, a total of 14 056 undergraduates (6862 males and 7194 females) aged 15-25 years participated in the study. RESULTS: After adjusting for multiple confounding factors, compared with the lowest quartile, the highest quartile intakes of pine nut (95 % CI (0·51, 0·98)) was significantly associated with 29 % reduction in hyperuricemia risk, the highest quartile intake of walnut (OR = 0·78; 95 % CI (0·58, 1·05)) was marginally negatively associated with hyperuricemia risk. CONCLUSIONS: The present study showed that the relationships between intakes of different nuts and hyperuricemia risk were different. Increased dietary intakes of walnut and pine nut are negatively associated with the hyperuricemia.
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Hiperuricemia , Nueces , Adolescente , Adulto , Estudios Transversales , Dieta , Ingestión de Alimentos , Femenino , Humanos , Hiperuricemia/epidemiología , Hiperuricemia/etiología , Masculino , Factores de Riesgo , Adulto JovenRESUMEN
Previous studies have shown that BMPR1B promotes follicular development and ovarian granulosa cell proliferation, thereby affecting ovulation in mammals. In this study, the expression and polymorphism of the BMPR1B gene associated with litter size in small-tail Han (STH) sheep were determined. The expression of BMPR1B was detected in 14 tissues of STH sheep during the follicular phase as well as in the hypothalamic-pituitary-gonadal (HPG) axis of monotocous and polytocous STH sheep during the follicular and luteal phases using quantitative polymerase chain reaction (qPCR). Sequenom MassARRAY® single nucleotide polymorphism (SNP) technology was also used to detect the polymorphism of SNPs in seven sheep breeds. Here, BMPR1B was highly expressed in hypothalamus, ovary, uterus, and oviduct tissue during the follicular phase, and BMPR1B was expressed significantly more in the hypothalamus of polytocous ewes than in monotocous ewes during both the follicular and luteal phases ( P < 0.05 ). For genotyping, we found that genotype and allele frequencies of three loci of the BMPR1B gene were extremely significantly different ( P < 0.01 ) between the monotocous and polytocous groups. Association analysis results showed that the g.29380965A > G locus had significant negative effects on the litter size of STH sheep, and the combination of g.29380965A > G and FecB (Fec - fecundity and B - Booroola; A746G) at the BMPR1B gene showed that the litter size of AG-GG, AA-GG, and GG-GG genotypes was significantly higher compared with other genotypes ( P < 0.05 ). This is the first study to find a new molecular marker affecting litter size and to systematically analyze the expression of BMPR1B in different fecundity and physiological periods of STH sheep.
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The results of randomized controlled trials (RCTs) investigating supplemental n-3 polyunsaturated fatty acids (PUFA) on muscle mass and function have been inconsistent. The present study aimed to quantitatively evaluate the effect of n-3 PUFA supplementation on indicators of muscle mass and function in healthy subjects. A systematic literature search was conducted up to July 2020 with databases of PubMed and Web of science. The random-effects model was implemented to calculate the weighted mean difference of net change of indicators regarding muscle mass and function. A total of nine studies (thirteen treatment groups) with 2067 participants were included for data analysis. The summary estimate showed that n-3 PUFA supplementation significantly increased the grip strength (1.17 kg; 95% CI: 0.27, 2.08 kg). Non-significant effect was observed with respect to muscle mass parameters, including fat mass (-0.67 kg; 95% CI: -2.20, 0.87 kg) and lean mass (0.33 kg; 95% CI: -0.35, 1.00 kg). Regarding muscle function indicators, there were non-significant effects on walking speed (-0.01 mâ¢s-1; 95% CI: -0.03, 0.01 mâ¢s-1), time up and go test (-0.25 s; 95% CI: -0.55, 0.04 s), respectively. The findings of this study indicated that supplementation with n-3 PUFA might have beneficial effects to improve muscle mass and function in healthy participants. However, there was no significant improvement in the subjects' muscle mass. Whether n-3 PUFA supplementation has favorable effects in participants with sarcopenia are warranted to be further investigated.
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Envejecimiento/fisiología , Ácidos Grasos Omega-3/administración & dosificación , Músculo Esquelético/fisiología , Envejecimiento/efectos de los fármacos , Ácidos Grasos Omega-3/farmacología , Fuerza de la Mano/fisiología , Humanos , Músculo Esquelético/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios de Tiempo y Movimiento , Velocidad al Caminar/efectos de los fármacosRESUMEN
To investigate the effect of ALA intake on blood lipid profiles, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein (VLDL-C) and ratio of TC to HDL-C. We systematically searched randomized controlled trials of ALA intervention on PubMed, Embase, Cochrane library and related references up to March 2018. The final values were calculated as weighted mean difference (WMD) by using a random effects model. Subgroup analysis and meta-regression were used to explore the source of heterogeneity. Generalized least square was performed for dose-response analysis. Forty-seven studies with 1305 individuals in the ALA arm and 1325 individuals in the control arm were identified. Compared with control group, dietary intake of ALA significantly reduced the concentrations of TG (WMD -0.101 mmol/L; 95% CI: -0.158 to -0.044 mmol/L; P = 0.001), TC (WMD -0.140 mmol/L; 95% CI: -0.224 to -0.056 mmol/L; P = 0.001), LDL-C (WMD -0.131 mmol/L; 95% CI: -0.191 to -0.071 mmol/L; P < 0.001), VLDL-C (WMD -0.121 mmol/L; 95% CI: -0.170 to -0.073 mmol/L; P < 0.001), TC/HDL-C ratio (WMD -0.165 mmol/L; 95% CI: -0.317 to -0.013 mmol/L; P = 0.033) and LDL-C/HDL-C ratio (WMD -0.158 mmol/L; 95% CI: -0.291 to -0.025 mmol/L; P = 0.02). There is no effect of ALA intake on HDL-C (WMD 0.008 mmol/L; 95% CI: -0.018 to 0.034 mmol/L; P = 0.541). Dose-response analysis indicated that 1 g per day increment of ALA was associated with a 0.0016 mmol/L, 0.0071 mmol/L, 0.0015 and 0.0061 mmol/L reduction in TG (95% CI: -0.0029 to -0.0002 mmol/L), TC (95% CI: -0.0085 to -0.0058 mmol/L), HDL-C (95% CI: -0.0020 to -0.0011 mmol/L) and LDL-C (95% CI: -0.0073 to -0.0049 mmol/L) levels, respectively. The effects of ALA intake on TG, TC and LDL-C concentrations were more obvious among Asian participants, and also more obvious on patients with hyperlipidemia or hyperglycemia compared to healthy individuals. Dietary ALA intervention improves blood lipid profiles by decreasing levels of TG, TC, LDL and VLDL-C. Our findings add to the evidence that increasing ALA intake could potentially prevent risk of cardiovascular diseases.
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Lípidos , Ácido alfa-Linolénico , HDL-Colesterol , LDL-Colesterol , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , TriglicéridosRESUMEN
The results of randomized controlled trials (RCTs) investigating supplemental vitamin D on aminotransferases and cardio-metabolic risk factors in subjects with non-alcoholic fatty liver disease (NAFLD) have been inconsistent. The present study aimed to quantitatively evaluate whether supplementation with vitamin D has beneficial effects in treatment of NAFLD. A systematical literature search was performed with Cochrane Library, PubMed, Scopus databases and Web of Science up to June 2020. The mean changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglyceride (TAG) were calculated as standard mean difference (SMD) using a random-effects model. Pre-specified subgroup and univariate meta-regression analyses were performed to identify the sources of heterogeneity. Ten trials with a total of 544 NAFLD subjects were included for data synthesis. The summary estimates indicated that supplemental vitamin D significantly reduced the levels of serum/plasma fasting glucose (-0.22; 95%CI: -0.39, -0.04), insulin (-0.68; 95%CI: -1.22, -0.14) and HOMA-IR (-1.32; 95%CI: -2.30, -0.34), and marginally reduced the ALT (-0.18; 95%CI: -0.39, 0.04) and TAG (-10.38; 95%CI: -21.09, 0.34) levels. However, the pooled effect did not support that supplemental vitamin D was beneficial for concentrations of AST, TC, HDL-C and LDL-C. The present study provides substantial evidence that supplemental vitamin D has favorable effects on glycemic control and insulin sensitivity in NAFLD patients. Vitamin D could be as an adjuvant pharmacotherapy of NAFLD.
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Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Vitamina D/administración & dosificación , Adulto , Anciano , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , Glucemia/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol , Suplementos Dietéticos/análisis , Femenino , Humanos , Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Triglicéridos/metabolismo , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: The association between circulating vitamin D and liver cancer risk has been controversial on the basis of epidemiological studies. The aim of this study was to quantitatively evaluate this association with prospective studies. METHODS AND STUDY DESIGN: A systematic literature search was implemented in PubMed and Scopus databases up to June 2019. Using a random-effects model, the multivariate-adjusted relative risks (RRs) with corresponding 95% confidence interval (CI) were pooled for the highest versus lowest category. Trend estimation was conducted with a two-stage dose-response meta-analysis. RESULTS: Six independent prospective studies (992 liver cancer events and 60,811 participants) were included for data synthesis. The summary estimate showed that a higher circulating vitamin D was associated with lower risk of liver cancer (Summary RR=0.78; 95% CI: 0.63, 0.95; I2=53.6%, p=0.035). Dose-response analysis indicated that liver cancer was associated with 8% (95% CI: 0.89, 0.95) lower risk with a 10 nmol/L increment of circulating vitamin D concentration. CONCLUSIONS: The present study provides substantial evidence that a higher concentration of circulating vitamin D would have conferred protection against liver cancer.