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1.
Am. j. clin. nutr ; 111(4): 795-803, abr., 2020. tab.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1051700

RESUMO

BACKGROUND: Eggs are a rich source of essential nutrients, but they are also a source of dietary cholesterol. Therefore, some guidelines recommend limiting egg consumption. However, there is contradictory evidence on the impact of eggs on diseases, largely based on studies conducted in high-income countries. OBJECTIVES: Our aim was to assess the association of egg consumption with blood lipids, cardiovascular disease (CVD), and mortality in large global studies involving populations from low-, middle-, and high-income countries. METHODS: We studied 146,011 individuals from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Egg consumption was recorded using country-specific validated FFQs. We also studied 31,544 patients with vascular disease in 2 multinational prospective studies: ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects with Cardiovascular Disease). We calculated HRs using multivariable Cox frailty models with random intercepts to account for clustering by study center separately within each study. RESULTS: In the PURE study, we recorded 14,700 composite events (8932 deaths and 8477 CVD events). In the PURE study, after excluding those with history of CVD, higher intake of egg (≥7 egg/wk compared with <1 egg/wk intake) was not significantly associated with blood lipids, composite outcome (HR: 0.96; 95% CI: 0.89, 1.04; P-trend = 0.74), total mortality (HR: 1.04; 95% CI: 0.94, 1.15; P-trend = 0.38), or major CVD (HR: 0.92; 95% CI: 0.83, 1.01; P-trend = 0.20). Similar results were observed in ONTARGET/TRANSCEND studies for composite outcome (HR 0.97; 95% CI: 0.76, 1.25; P-trend = 0.09), total mortality (HR: 0.88; 95% CI: 0.62, 1.24; P-trend = 0.55), and major CVD (HR: 0.97; 95% CI: 0.73, 1.29; P-trend = 0.12). CONCLUSIONS: In 3 large international prospective studies including ∼177,000 individuals, 12,701 deaths, and 13,658 CVD events from 50 countries in 6 continents, we did not find significant associations between egg intake and blood lipids, mortality, or major CVD events. (AU)


Assuntos
Colesterol na Dieta , Doenças Cardiovasculares , Mortalidade
2.
Zhonghua Gan Zang Bing Za Zhi ; 28(3): 203-207, 2020 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-32306652

RESUMO

Non-alcoholic fatty liver disease and obesity have interconnected genes, but it can also occur in non-obese population with body mass index < 25 kg/m(2). Non-obese type of non-alcoholic fatty liver disease mostly occurs in Asia. There is no significant difference between obese and non-obese type of non-alcoholic fatty liver in histological examination of liver biopsies. Visceral obesity, high fructose and cholesterol intake, and genetic factors such as APOC3 gene mutation are closely related to non-obese type of non-alcoholic fatty liver. Generally speaking, non-alcoholic steatohepatitis has an increased mortality rate, mainly due to cardiovascular causes, and has no link with other metabolic factors. Although data on the impact of mortality from non-obese type of non-alcoholic fatty liver disease are incomplete and limited, however diagnosis, management, and treatment may be important. Lifestyle changes to reduce visceral obesity, including dietary changes and physical activity, remain the main treatment options for patients with non-obese type of non-alcoholic fatty liver disease.


Assuntos
Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade , Apolipoproteína C-III/genética , Índice de Massa Corporal , Colesterol na Dieta , Frutose , Humanos , Estilo de Vida , Hepatopatia Gordurosa não Alcoólica/mortalidade , Obesidade Abdominal , Fatores de Risco
3.
PLoS One ; 15(3): e0229669, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163433

RESUMO

Exogenously hypercholesterolemic (ExHC) rats develop diet-induced hypercholesterolemia (DIHC) when fed with dietary cholesterol. Previously, we reported that, under the high-sucrose-diet-feeding condition, a loss-of-function mutation in Smek2 results in low activity of fatty acid synthase (FAS) followed by the shortage of hepatic triacylglycerol content in ExHC rats and the onset of DIHC. However, the relationship between the Smek2 mutation and FAS dysfunction is still unclear. Here, we focused on carbohydrate metabolism, which provides substrates for FAS, and analyzed carbohydrate and lipid metabolisms in ExHC rats to clarify how the deficit of Smek2 causes DIHC. Male ExHC and SD rats were fed high-sucrose or high-starch diets containing 1% cholesterol for 2 weeks. Serum cholesterol levels of the ExHC rats were higher, regardless of the dietary carbohydrate. Hepatic triacylglycerol levels were higher in only the SD rats fed the high-sucrose diet. Moreover, the ExHC rats exhibited a diabetes-like status and accumulation of hepatic glycogen and low hepatic mRNA levels of liver-type phosphofructokinase (Pfkl), which encodes a rate-limiting enzyme for glycolysis. These results suggest that the glucose utilization, particularly glycolysis, is impaired in the liver of ExHC rats. To evaluate how the diet with extremely low glucose affect to DIHC, ExHC.BN-Dihc2BN, a congenic strain that does not develop DIHC, and ExHC rats were fed a high-fructose diet containing 1% cholesterol for 2 weeks. The serum cholesterol and hepatic triacylglycerol levels were similar in the strains. Results of water-soluble metabolite analysis with primary hepatocytes, an increase in fructose-6-phosphate and decreases in succinate, malate and aspartate in ExHC rats, support impaired glycolysis in the ExHC rats. Thus, the Smek2 mutation causes abnormal hepatic glucose utilization via downregulation of Pfkl expression. This abnormal glucose metabolism disrupts hepatic fatty acid synthesis and causes DIHC in the ExHC rats.


Assuntos
Glucose/metabolismo , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Fígado/metabolismo , Animais , Animais Congênicos , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/efeitos adversos , Modelos Animais de Doenças , Regulação para Baixo , Ácido Graxo Sintase Tipo I/metabolismo , Glicólise/genética , Hipercolesterolemia/genética , Mutação com Perda de Função , Masculino , Fosfofrutoquinases/genética , Fosfofrutoquinases/metabolismo , Fosfoproteínas Fosfatases/deficiência , Fosfoproteínas Fosfatases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Sprague-Dawley
5.
Life Sci ; 250: 117514, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32145306

RESUMO

AIMS: Pigs are increasingly used as human metabolic disease models; however, there is insufficient research on breed-related genetic background differences. This study aimed to investigate the differential metabolic responses to high-fat and high-cholesterol (HFC) diet-induced non-alcoholic fatty liver disease (NAFLD) of two miniature pig breeds and explore the molecular mechanisms involved. MAIN METHODS: Male Wuzhishan (WZSP) and Tibetan pigs (TP) were randomly fed either a standard or an HFC diet for 24 weeks. Weight, serum lipids, bile acid, insulin resistance, liver function, liver histology, and hepatic lipid deposition were determined. RNA-Seq was used to detect the hepatic gene expression profiles. Western blot, immunohistochemistry, and qRT-PCR were used to detect the lipid and glucose metabolism-related gene expressions. KEY FINDINGS: The HFC diet caused obesity, hypertension, severe hypercholesterolemia, liver injury, increased hepatocellular steatosis and inflammation, and significantly increased serum insulin levels in both pig breeds. This diet led to higher serum and hepatic cholesterol level concentrations in WZSP and elevated fasting glucose levels in TP. Transcriptome analysis revealed that the genes controlling hepatic cholesterol metabolism and the inflammatory response were consistently regulated; lipid metabolism and insulin signaling related genes were uniquely regulated by the HFC diet in the WZSP and TP, respectively. SIGNIFICANCE: Our study demonstrated that the genetic background affects profoundly pigs' metabolic and hepatic responses to an HFC diet. These results deepened our understanding of the molecular mechanisms of HFC diet-induced NAFLD and provided a foundation for selecting the appropriate pig breeds for metabolic studies in the future.


Assuntos
Ração Animal , Colesterol na Dieta , Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Transcriptoma , Animais , Glicemia/análise , Colesterol/metabolismo , Modelos Animais de Doenças , Biblioteca Gênica , Hipercolesterolemia/etiologia , Hiperlipidemias/etiologia , Hipertensão/etiologia , Inflamação/etiologia , Insulina/metabolismo , Fígado/metabolismo , Hepatopatias/etiologia , Masculino , Obesidade/etiologia , Fenótipo , Distribuição Aleatória , Especificidade da Espécie , Suínos , Porco Miniatura
6.
Life Sci ; 243: 117275, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31926242

RESUMO

AIMS: Imatinib is an effective tyrosine kinase inhibitor which has different therapeutic actions. The recent work demonstrated the possible beneficial effects of imatinib on the progression of atherosclerosis, endothelial dysfunction, and hypercholesterolemia-associated liver damage in rabbits. MAIN METHODS: Animals had been distributed in 4 groups: group 1 (non-treated): animals fed regular diet; group 2 high cholesterol [HC]: animals fed 1% cholesterol supplemented diet for 30 days; group 3 (HC-Imatinib): animals fed 1% cholesterol supplemented diet+imatinib (0.01 g/kg daily, p.o) for 30 days; group 4 (Imatinib): animals fed regular diet with imatinib (0.01 g/kg daily, p.o). After thirty days, tissue samples and blood were isolated to be detected biochemically, histologically, and for in vitro analysis. KEY FINDINGS: HC exhibited significant elevations in serum lipid parameters, CRP, ALT, AST and ALP. Additionally, HC induced significant increases for aortic and hepatic MDA, aortic NO and hepatic PDGFR-ß, while significantly exhibited reductions in aortic and hepatic GSH, SOD and hepatic PPARγ1. Moreover, HC produced impairment in ACh-enhanced aortic relaxation and aortic pathological changes. Histopathological examination of HC-fed rabbits revealed hepatic steatosis compared with non-treated group. Imatinib administration exhibited significant decreases in serum lipid parameters, CRP, ALT, AST and ALP. Additionally, imatinib induced significant decreases for aortic and hepatic MDA, aortic NO and hepatic PDGFR-ß, while significantly exhibited elevations in aortic and hepatic GSH, SOD and hepatic PPARγ1 compared with HC animals. Furthermore, imatinib significantly protected against HC produced attenuation in ACh-induced aortic relaxation and pathological changes in aortic and hepatic tissues. Interestingly, imatinib could return serum CRP, ALP, hepatic SOD and PDGFR-ß to basal values. SIGNIFICANCE: The recent observation reports that imatinib could have beneficial effect against atherosclerosis progression, vascular malfunction, and liver damage in high cholesterol diet (HCD)-fed rabbits.


Assuntos
Aterosclerose/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Hipercolesterolemia/complicações , Mesilato de Imatinib/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/patologia , Animais , Aorta/enzimologia , Aorta/metabolismo , Aorta/patologia , Aterosclerose/etiologia , Peso Corporal , Proteína C-Reativa/metabolismo , Colesterol na Dieta/administração & dosagem , Dieta , Endotélio Vascular/fisiopatologia , Enzimas/sangue , Enzimas/metabolismo , Mesilato de Imatinib/farmacologia , Lipídeos/sangue , Masculino , Coelhos
7.
Metabolism ; 104: 154140, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31926204

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases that may progress to liver fibrosis or cancer. The present study aimed to investigate the role of microRNA-125b-5p (miR-125b-5p) in NAFLD and to further explore underlying molecular mechanisms. METHODS: A mouse model of NAFLD was constructed by high cholesterol diet feeding and a cell-model was developed by treating the mouse liver cell line NCTC1469 with palmitic acid. Gain- and loss-of-function experiments were performed to determine the effects of miR-125b-5p, integrin α8 (ITGA8), and the RhoA signaling pathway on liver fibrosis in NAFLD. After the expression levels of miR-125b-5p, ITGA8, and RhoA were determined, liver fibrosis was evaluated in vivo and in vitro. The binding relationship of miR-125b-5p and ITGA8 was then validated. Finally, miR-125b-5p promoter methylation in NAFLD liver tissues and cells was determined. RESULTS: In NAFLD clinical samples, mouse model, and cell-model, miR-125b-5p expression was reduced, while ITGA8 expression was increased. Moreover, miR-125b-5p targeted and downregulated ITGA8, leading to inhibition of the RhoA signaling pathway. In NAFLD liver tissues and cells, the CpG island in the miR-125b-5p promoter was methylated, causing epigenetic silencing of miR-125b-5p. Both miR-125b-5p silencing and ITGA8 overexpression promoted in vitro and in vivo liver fibrosis in NAFLD via activation of the RhoA signaling pathway. CONCLUSIONS: Collectively, epigenetic silencing of miR-125b-5p upregulates ITGA8 expression to activate the RhoA signaling pathway, leading to liver fibrosis in NAFLD.


Assuntos
Epigênese Genética , Cadeias alfa de Integrinas/genética , Cirrose Hepática/genética , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Linhagem Celular , Colesterol na Dieta , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Transdução de Sinais/genética
8.
Gut ; 69(3): 551-563, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31076404

RESUMO

OBJECTIVE: Bone marrow-derived myeloid cells accumulate in the liver as monocytes and macrophages during the progression of obesity-related non-alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH). Myeloid cells comprise heterogeneous subsets, and dietary overnutrition may affect macrophages in the liver and bone marrow. We therefore aimed at characterising in depth the functional adaptations of myeloid cells in fatty liver. DESIGN: We employed single-cell RNA sequencing to comprehensively assess the heterogeneity of myeloid cells in the liver and bone marrow during NAFLD, by analysing C57BL/6 mice fed with a high-fat, high-sugar, high-cholesterol 'Western diet' for 16 weeks. We also characterised NAFLD-driven functional adaptations of macrophages in vitro and their functional relevance during steatohepatitis in vivo. RESULTS: Single-cell RNA sequencing identified distinct myeloid cell clusters in the liver and bone marrow. In both compartments, monocyte-derived populations were largely expanded in NASH-affected mice. Importantly, the liver myeloid compartment adapted a unique inflammatory phenotype during NAFLD progression, exemplarily characterised by downregulated inflammatory calprotectin (S100A8/A9) in macrophage and dendritic cell subsets. This distinctive gene signature was also found in their bone marrow precursors. The NASH myeloid phenotype was principally recapitulated by in vitro exposure of bone marrow-derived macrophages with fatty acids, depended on toll-like receptor 4 signalling and defined a characteristic response pattern to lipopolysaccharide stimulation. This imprinted and stable NASH myeloid immune phenotype functionally determined inflammatory responses following acute liver injury (acetaminophen poisoning) in vivo. CONCLUSION: Liver myeloid leucocytes and their bone marrow precursors adapt a common and functionally relevant inflammatory signature during NAFLD progression.


Assuntos
Medula Óssea/patologia , Fígado/patologia , Células Mieloides/imunologia , Células Mieloides/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Calgranulina A/genética , Calgranulina B/genética , Colesterol na Dieta/administração & dosagem , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Modelos Animais de Doenças , Regulação para Baixo , Expressão Gênica , Inflamação/imunologia , Inflamação/patologia , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Monócitos/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Fenótipo , Análise de Sequência de RNA , Transdução de Sinais , Análise de Célula Única , Receptor 4 Toll-Like/metabolismo
9.
Am J Physiol Endocrinol Metab ; 318(2): E249-E261, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31846369

RESUMO

Hepatic fat-specific protein 27 [cell death-inducing DNA fragmentation effector protein C (Cidec)/Fsp27] mRNA levels have been associated with hepatic lipid droplet extent under certain circumstances. To address its hepatic expression under different dietary conditions and in both sexes, apolipoprotein E (Apoe)-deficient mice were subjected to different experimental conditions for 11 wk to test the influence of cholesterol, Western diet, squalene, oleanolic acid, sex, and surgical castration on Cidec/Fsp27 mRNA expression. Dietary cholesterol increased hepatic Cidec/Fsp27ß expression, an effect that was suppressed when cholesterol was combined with saturated fat as represented by Western diet feeding. Using the latter diet, neither oleanolic acid nor squalene modified its expression. Females showed lower levels of hepatic Cidec/Fsp27ß expression than males when they were fed Western diets, a result that was translated into a lesser amount of CIDEC/FSP27 protein in lipid droplets and microsomes. This was also confirmed in low-density lipoprotein receptor (Ldlr)-deficient mice. Incubation with estradiol resulted in decreased Cidec/Fsp27ß expression in AML12 cells. Whereas male surgical castration did not modify the expression, ovariectomized females did show increased levels compared with control females. Females also showed increased expression of peroxisome proliferator-activated receptor-γ coactivator 1-α (Pgc1a), suppressed by ovariectomy, and the values were significantly and inversely associated with those of Cidec/Fsp27ß. When Pgc1a-deficient mice were used, the sex differences in Cidec/Fsp27ß expression disappeared. Therefore, hepatic Cidec/Fsp27ß expression has a complex regulation influenced by diet and sex hormonal milieu. The mRNA sex differences are controlled by Pgc1a.


Assuntos
Dieta Ocidental/efeitos adversos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas/genética , Animais , Linhagem Celular , Colesterol na Dieta/farmacologia , Feminino , Gotículas Lipídicas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , Orquiectomia , Ovariectomia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , RNA Mensageiro/biossíntese , Receptores de LDL/genética , Receptores de LDL/metabolismo , Caracteres Sexuais
10.
PLoS One ; 14(12): e0225857, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31790488

RESUMO

Although the high-fat-diet-induced metabolic syndrome (MetS) is a precursor of human cardiac pathology, the myocardial metabolic state in MetS is far from clear. The discrepancies in metabolite handling between human and small animal models and the difficulties inherent in obtaining human tissue complicate the identification of the myocardium-specific metabolic response in patients. Here we use the large animal model of swine that develops the hallmark criteria of human MetS. Our comparative metabolomics together with transcriptomics and computational nonnegative matrix factorization (NMF) interpretation of the data exposes significant decline in metabolites related to the fatty acid oxidation, glycolysis, and pentose phosphate pathway. Behind the reversal lies decreased expression of enzymes that operate in the pathways. We showed that diminished glycogen deposition is a metabolic signature of MetS in the pig myocardium. The depletion of glycogen arises from disbalance in expression of genes that break down and synthesize glycogen. We show robust acetoacetate accumulation and activated expression of key enzymes in ketone body formation, catabolism and transporters, suggesting a shift in fuel utilization in MetS. A contrasting enrichment in O-GlcNAcylated proteins uncovers hexosamine pathway and O-GlcNAcase (OGA) expression involvement in the myocardial response to MetS. Although the hexosamine biosynthetic pathway (HBP) activity and the availability of the UDP-GlcNAc substrate in the MetS myocardium is low, the level of O-GlcNacylated proteins is high as the O-GlcNacase is significantly diminished. Our data support the perception of transcriptionally driven myocardial alterations in expression of standard fatty acids, glucose metabolism, glycogen, and ketone body related enzymes and subsequent paucity of their metabolite products in MetS. This aberrant energy metabolism in the MetS myocardium provide insight into the pathogenesis of CVD in MetS.


Assuntos
Redes e Vias Metabólicas , Síndrome Metabólica/metabolismo , Miocárdio/metabolismo , Animais , Colesterol na Dieta/efeitos adversos , Dieta , Glicosilação , Masculino , Metaboloma , Metabolômica , N-Acetilglucosaminiltransferases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Risco , Suínos , Aprendizado de Máquina não Supervisionado , beta-N-Acetil-Hexosaminidases/metabolismo
11.
Lipids Health Dis ; 18(1): 218, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829191

RESUMO

BACKGROUND: The cholesterol gallstones diseases (CGD) is highly correlated with metabolic syndrome and type 2 diabetes. The present study aimed to investigate preventive effects of pioglitazone (PIO), an antidiabetic drug, on the CGD in guinea pigs fed with a lithogenic diet (LD). METHODS: The guinea pigs were fed with the LD for 8 weeks. All guinea pigs were grouped as follows: low fat diet; LD; LD plus PIO (4 mg/kg); LD plus PIO (8 mg/kg); LD plus ezetimibe (EZE) (2 mg/kg). Gallbladder stones were observed using microscopy. The profile of biliary composition, and blood glucose, insulin and lipid were analyzed. The liver or ileum was harvested for determinations of hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7α-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8), bile salt export pump (BSEP), Niemann-Pick C1-Like 1 (NPC1L1) and acetyl-coenzyme A cholesterol acyltransferase (ACAT2) by Western blot. The gallbladders were used for histological examination. RESULTS: The LD successfully induced gallstone. Both pioglitazone and ezetimibe prevented gallstone formation, as well as hepatic and cholecystic damages. Pioglitazone significantly decreased HMGCR and SREBP2, but increased CYP7A1, ABCG5, ABCG8, and BSEP in the liver. Pioglitazone also remarkably decreased NPC1L1 and ACAT2, while increased ABCG5/8 in the intestine. The beneficial alterations of cholesterol and bile acids in the bile, as well as profile of glucose, insulin and lipid in the blood were found in the guinea pigs treated with pioglitazone. CONCLUSION: Pioglitazone has a noticeable benefit towards the CGD, which is involved in changes of synthesis, transformation, absorption, and transportation of cholesterol.


Assuntos
Ácidos e Sais Biliares/administração & dosagem , Colesterol na Dieta/administração & dosagem , Colesterol/metabolismo , Cálculos Biliares/prevenção & controle , Homeostase/efeitos dos fármacos , Pioglitazona/administração & dosagem , Transportadores de Cassetes de Ligação de ATP/análise , Animais , Anticolesterolemiantes , Colesterol 7-alfa-Hidroxilase/análise , Dieta , Ezetimiba/administração & dosagem , Vesícula Biliar/química , Vesícula Biliar/metabolismo , Vesícula Biliar/patologia , Cálculos Biliares/etiologia , Cobaias , Hidroximetilglutaril-CoA Redutases/análise , Hipoglicemiantes , Fígado/química , Fígado/metabolismo , Fígado/patologia , Masculino , Proteína de Ligação a Elemento Regulador de Esterol 2/análise
12.
Nutrients ; 11(12)2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31783560

RESUMO

The association of dietary cholesterol intake with dyslipidemia and subtypes is controversial. This study aimed to examine the association of dietary cholesterol intake with dyslipidemia and subtypes in Chinese adults. Using data from the China Health and Nutrition Survey (CHNS) in 2015, the present study selected 4383 participants aged 18-59 years who were free of diabetes, apoplexy, and myocardial infarction disease. Information was obtained on dietary intake, anthropometric measurements, and blood laboratory measurements. Dietary cholesterol intake was calculated based on the data collected by consecutive 3 days 24 h recalls combined with the weighing of household seasonings and categorized by 11 levels: The first 10 levels in ranges of 50 mg/day and the 11th level at ≥500 mg/day. Dyslipidemia, hypercholesterolemia, hypertriglyceridemia, low-density lipoprotein (LDL)-hypercholesterolemia, and high-density lipoprotein (HDL)-hypocholesterolemia were defined based on the Chinese adult dyslipidemia prevention guide (2016 edition). Multivariable logistic regressions were performed to examine the association of dietary cholesterol intake levels with dyslipidemia and subtypes. The prevalence of dyslipidemia was 37.5% among Chinese adults in 2015 (hypercholesterolemia 9.6%, HDL-hypocholesterolemia 21.1%, LDL-hypercholesterolemia 12.7%, and hypertriglyceridemia 15.2%). The lowest prevalence of hypercholesterolemia and LDL-hypercholesterolemia was 6.7% and 9.4%, respectively, which was relative to a dietary cholesterol intake level of 100.0 to <150.0 mg/day. After adjusting for all potential confounders, adults with the highest dietary cholesterol intake level of ≥500 mg/day compared with the dietary cholesterol intake of 100.0 to <150.0 mg/day showed one-time higher odds of hypercholesterolemia (odds ratios (OR) 2.0, 95% confidence intervals (CI) 1.3-3.3), as well as LDL-hypercholesterolemia (OR 2.0, 95% CI 1.3-3.0), but a null association of dietary cholesterol intake with dyslipidemia, hypertriglyceridemia, and HDL-hypocholesterolemia. The study suggested that a dietary cholesterol intake level of 500 mg/day and above may be a threshold point for high odds of hypercholesterolemia and LDL-hypercholesterolemia.


Assuntos
Colesterol na Dieta/administração & dosagem , Dislipidemias/epidemiologia , Inquéritos Nutricionais , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Registros de Dieta , Humanos , Hipercolesterolemia/epidemiologia , Hipertrigliceridemia/epidemiologia , Pessoa de Meia-Idade , Razão de Chances , Adulto Jovem
13.
Oxid Med Cell Longev ; 2019: 4521786, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885793

RESUMO

Lipid metabolic disorders due to poor eating habits are on the rise in both developed and developing countries, with a negative impact of the "Western diet" on sperm count and quality. Dietary lipid imbalance can involve cholesterol, fatty acids, or both, under different pathophysiological conditions grouped under the term dyslipidemia. The general feature of dyslipidemia is the development of systemic oxidative stress, a well-known deleterious factor for the quality of male gametes and associated with infertility. Sperm are particularly rich in polyunsaturated fatty acids (PUFA), an important characteristic associated with normal sperm physiology and reproductive outcomes, but also targets of choice for oxidative thrust. This review focuses on the effects of dietary cholesterol or different fatty acid overload on sperm composition and function in both animals and humans. The links between oxidative stress induced by dyslipidemia and sperm dysfunction are then discussed, including possible preventive or therapeutic strategies to preserve gamete quality, longevity when stored in cryobanking, and male fertility.


Assuntos
Colesterol na Dieta/metabolismo , Fertilidade/fisiologia , Lipídeos/fisiologia , Estresse Oxidativo/fisiologia , Animais , Modelos Animais de Doenças , Humanos , Masculino
14.
Nutrients ; 11(11)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731675

RESUMO

Soybean germ phytosterols (SGP) largely exist in soybean germ oil. Our previous study demonstrated that soybean germ oil was effective in reducing plasma cholesterol. However, it remains unknown if its phytosterols are the active ingredients responsible for the plasma cholesterol-lowering activity. The present study aimed to test the effect of SGP on plasma cholesterol and to investigate its associated underlying mechanisms using hamsters as animal model. Male hamsters (n = 40) were randomly divided into five groups (n = 8/group) and fed one of the five diets: a non-cholesterol diet (NCD), a high cholesterol diet (HCD), a HCD diet containing 0.5% cholestyramine (PC), and two HCD diets containing 0.1% (LP) and 0.2% (HP) SGP, respectively, for six weeks. Results showed that SPG reduced plasma cholesterol level in a dose-dependent manner, whereas it dose-dependently increased the excretion of both fecal neutral and acidic sterols. SGP was also effective in displacing cholesterol from micelles. It was concluded that SGP possessed hypocholesterolemic activity, likely by inhibiting cholesterol absorption in the intestine and promoting fecal sterol excretion.


Assuntos
Anticolesterolemiantes/farmacologia , Colesterol na Dieta/farmacologia , Colesterol/sangue , Dieta/efeitos adversos , Fitosteróis/farmacologia , Óleo de Soja/química , Animais , Cricetinae , Dieta/métodos , Fezes/química , Intestinos/efeitos dos fármacos , Masculino , Esteróis/análise
16.
Pathol Res Pract ; 215(11): 152599, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31564568

RESUMO

Understanding of the pathogenesis of nonalcoholic steatohepatitis (NASH)-associated fibrosis has been hampered by the lack of a comprehensive and physiological small animal model of NASH with fibrosis. Feeding a high-fat and high-cholesterol (HFC) diet supplemented with cholic acid to rats is known to replicate human NASH pathology, and it induces fibrosis earlier than with an HFC diet alone. In the present study, physiological and histopathological observations from 65 Sprague-Dawley (SD) rats fed an HFC diet with or without cholic acid for 9 or 18 weeks in our laboratory between January 2013 and February 2018 were retrospectively reviewed. The liver weight/body weight ratio at the end of the rearing period was higher in rats fed an HFC diet than in rats fed a normal diet in a cholesterol dose-, cholic acid dose-, or rearing period dependent manner. Dietary fat, cholesterol and/or cholic acid and rearing period affected the histopathologic severity of NASH. Overall, 56 (86.2%) of 65 SD rats fed an HFC diet for 9 or 18 weeks developed histopathologically proven NASH. It is noted that the SD rats fed an HFC diet supplemented with 2% (w/w) cholic acid for 18 weeks frequently developed advanced fibrosis, including cirrhosis. Thus, this diet-induced NASH rat model is likely to be a highly reproducible.


Assuntos
Colesterol na Dieta/toxicidade , Ácido Cólico/toxicidade , Gorduras na Dieta/toxicidade , Modelos Animais de Doenças , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cirrose Hepática Experimental/etiologia , Cirrose Hepática Experimental/patologia , Ratos , Ratos Sprague-Dawley
17.
J Food Sci ; 84(11): 3075-3082, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31599971

RESUMO

The hypocholesterolemic effect of amaranth was studied in male Wistar rats fed a high-fat diet that was supplemented with amaranth flour, AF, or isolated protein, AI. Likewise, an in vitro test was carried out, in which the capacity of the AI, AF, the digested isolate, DAI, and the digested amaranth flour, DAF, to displace the cholesterol of the model micelles was evaluated. The in vivo results showed an increase in the excretion of cholesterol through feces (77% for AF7; 23% and 108% for AI30 and AF30, respect control) and a decrease in the content of hepatic cholesterol (98% for AF7; 96% and 53% for AI30 and AF30 respect control); whereas in vitro it was shown that both AF and DAF have greater power to displace cholesterol than the AI and DAI (IC50 0.1, 0.71, 0.2, and 2.1 for AF, DAF, AI, and DAI, respectively). These evidences show that the proteins and fibers of amaranth have an effect on cholesterol metabolism. PRACTICAL APPLICATION: Nowadays, consumers give great importance to the effect that food has on health. The results shown in this work evidence the potential hypocholesterolemic activity presented by amaranth, this is of great importance due to the increase in the incidence of dyslipidemia in the world population and the importance of amaranth as a nonextensive crop of excellent agronomic, nutritional, and bioactive properties suitable for preparation of functional foods.


Assuntos
Amaranthus/química , Anticolesterolemiantes/administração & dosagem , Dieta Hiperlipídica , Animais , Anticolesterolemiantes/análise , Colesterol/análise , Colesterol/metabolismo , Colesterol na Dieta , Fezes/química , Fígado/química , Masculino , Ratos , Ratos Wistar
18.
World J Gastroenterol ; 25(39): 5936-5952, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660031

RESUMO

BACKGROUND: The use of methyl-tertiary butyl ether (MTBE) to dissolve gallstones has been limited due to concerns over its toxicity and the widespread recognition of the safety of laparoscopic cholecystectomy. The adverse effects of MTBE are largely attributed to its low boiling point, resulting in a tendency to evaporate. Therefore, if there is a material with a higher boiling point and similar or higher dissolubility than MTBE, it is expected to be an attractive alternative to MTBE. AIM: To determine whether tert-amyl ethyl ether (TAEE), an MTBE analogue with a relatively higher boiling point (102 °C), could be used as an alternative to MTBE in terms of gallstone dissolubility and toxicity. METHODS: The in vitro dissolubility of MTBE and TAEE was determined by measuring the dry weights of human gallstones at predetermined time intervals after placing them in glass containers with either of the two solvents. The in vivo dissolubility was determined by comparing the weights of solvent-treated gallstones and control (dimethyl sulfoxide)-treated gallstones, after the direct infusion of each solvent into the gallbladder in both hamster models with cholesterol and pigmented gallstones. RESULTS: The in vitro results demonstrated a 24 h TAEE-dissolubility of 76.7%, 56.5% and 38.75% for cholesterol, mixed, and pigmented gallstones, respectively, which represented a 1.2-, 1.4-, and 1.3-fold increase in dissolubility compared to that of MTBE. In the in vitro experiment, the 24 h-dissolubility of TAEE was 71.7% and 63.0% for cholesterol and pigmented gallstones, respectively, which represented a 1.4- and 1.9-fold increase in dissolubility compared to that of MTBE. In addition, the results of the cell viability assay and western blot analysis indicated that TAEE had a lower toxicity towards gallbladder epithelial cells than MTBE. CONCLUSION: We demonstrated that TAEE has higher gallstone dissolubility properties and safety than those of MTBE. As such, TAEE could present an attractive alternative to MTBE if our findings regarding its efficacy and safety can be consistently reproduced in further subclinical and clinical studies.


Assuntos
Éter/administração & dosagem , Cálculos Biliares/terapia , Éteres Metílicos/administração & dosagem , Solventes/administração & dosagem , Animais , Sobrevivência Celular/efeitos dos fármacos , Colesterol na Dieta/efeitos adversos , Dieta da Carga de Carboidratos/efeitos adversos , Modelos Animais de Doenças , Éter/efeitos adversos , Feminino , Cálculos Biliares/diagnóstico por imagem , Cálculos Biliares/etiologia , Humanos , Mesocricetus , Éteres Metílicos/efeitos adversos , Solventes/efeitos adversos , Resultado do Tratamento , Ultrassonografia
19.
J Nutr Sci Vitaminol (Tokyo) ; 65(4): 349-356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474685

RESUMO

Nonalcoholic steatohepatitis (NASH), a subtype of nonalcoholic fatty liver disease (NAFLD), has a potentially progressive course that can lead to liver cirrhosis. Age is strongly associated with the development and progression of NAFLD/NASH, but the natural history of pediatric NAFLD is still not fully understood. Here, we evaluated the age-related alterations of NASH in 5-, 9- and 13-wk-old male Sprague-Dawley rats that were fed a high-fat and high-cholesterol diet (30% fat, 1.25% cholesterol and 0.5% sodium cholate, w/w) for 9 wk (6 rats/group). Our results showed that the cumulative energy intake, body weight gain and food efficacy during the 9-wk rearing period were highest in the youngest group and lowest in the oldest group. Serologically, almost all parameters including the serum triglyceride and total cholesterol were similar regardless of age. Histopathological findings, such as hepatic steatosis, lobular inflammation and hepatocyte ballooning, were also similar regardless of age, but hepatic fibrosis was more evident in the oldest group. Also, the mRNA expression levels of some fibrogenic, inflammatory, oxidative stress and cholesterol or lipid metabolism-related genes in the liver were highest in the oldest group and lowest in the youngest group, although the difference was not statistically significant. These results indicated that aging is likely associated with the development of NASH. Because the cumulative energy intake and daily food intake/body weight were not similar among groups in the present study, further studies designed with an equivalent daily food intake/body weight among groups are needed in order to interpret the exact nutritional effect.


Assuntos
Envelhecimento/fisiologia , Colesterol na Dieta/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Colesterol na Dieta/administração & dosagem , Ingestão de Alimentos , Ingestão de Energia , Expressão Gênica , Inflamação/genética , Metabolismo dos Lipídeos/genética , Lipídeos/sangue , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Estresse Oxidativo/genética , Ratos , Ratos Sprague-Dawley
20.
PLoS One ; 14(9): e0223019, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31539420

RESUMO

Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide. While it has been suggested to cause nervous impairment, its neurophysiological basis remains unknown. Therefore, the aim of this study is to unravel the effects of NASH, through the interrelationship of liver, gut microbiota, and nervous system, on the brain and human behavior. To this end, 40 Sprague-Dawley rats were divided into a control group that received normal chow and a NASH group that received a high-fat, high-cholesterol diet. Our results show that 14 weeks of the high-fat, high-cholesterol diet induced clinical conditions such as NASH, including steatosis and increased levels of ammonia. Rats in the NASH group also demonstrated evidence of gut dysbiosis and decreased levels of short-chain fatty acids in the gut. This may explain the deficits in cognitive ability observed in the NASH group, including their depressive-like behavior and short-term memory impairment characterized in part by deficits in social recognition and prefrontal cortex-dependent spatial working memory. We also reported the impact of this NASH-like condition on metabolic and functional processes. Brain tissue demonstrated lower levels of metabolic brain activity in the prefrontal cortex, thalamus, hippocampus, amygdala, and mammillary bodies, accompanied by a decrease in dopamine levels in the prefrontal cortex and cerebellum and a decrease in noradrenalin in the striatum. In this article, we emphasize the important role of ammonia and gut-derived bacterial toxins in liver-gut-brain neurodegeneration and discuss the metabolic and functional brain regional deficits and behavioral impairments in NASH.


Assuntos
Encéfalo/metabolismo , Transtornos Cognitivos/metabolismo , Disbiose/metabolismo , Microbioma Gastrointestinal , Hiperamonemia/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Colesterol na Dieta/efeitos adversos , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/microbiologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Disbiose/microbiologia , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Ratos Sprague-Dawley
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