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1.
Molecules ; 26(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34443451

RESUMO

Diabetes mellitus is characterized by tissue oxidative damage and impaired microcirculation, as well as worsened erythrocyte properties. Measurements of erythrocyte deformability together with determination of nitric oxide (NO) production and osmotic resistance were used for the characterization of erythrocyte functionality in lean (control) and obese Zucker diabetic fatty (ZDF) rats of two age categories. Obese ZDF rats correspond to prediabetic (younger) and diabetic (older) animals. As antioxidants were suggested to protect erythrocytes, we also investigated the potential effect of quercetin (20 mg/kg/day for 6 weeks). Erythrocyte deformability was determined by the filtration method and NO production using DAF-2DA fluorescence. For erythrocyte osmotic resistance, we used hemolytic assay. Erythrocyte deformability and NO production deteriorated during aging-both were lower in older ZDF rats than in younger ones. Three-way ANOVA indicates improved erythrocyte deformability after quercetin treatment in older obese ZDF rats only, as it was not modified or deteriorated in both (lean and obese) younger and older lean animals. NO production by erythrocytes increased post treatment in all experimental groups. Our study indicates the potential benefit of quercetin treatment on erythrocyte properties in condition of diabetes mellitus. In addition, our results suggest potential age-dependency of quercetin effects in diabetes that deserve additional research.


Assuntos
Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Eritrócitos/metabolismo , Quercetina/uso terapêutico , Animais , Antioxidantes , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Deformação Eritrocítica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Óxido Nítrico/metabolismo , Osmose , Estresse Oxidativo , Quercetina/farmacologia , Ratos Zucker
2.
Nutrients ; 13(8)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34444691

RESUMO

The aim of the report was to evaluate the impact of soy protein containing isoflavones and soy isoflavones extract on lipid profile in postmenopausal women, as compared with placebo or protein of milk, casein or isolated soy protein with or without trace isoflavone content. We used the following databases: MEDLINE (PubMed), EMBASE and the Cochrane Library. Quantitative data synthesis was performed by applying a random-effects model. Subgroup analysis and meta-regression were performed to assess the modifiers of treatment response. In total, in the analysis studies, 2305 postmenopausal women took part. Changes in the lipid profile showed statistically significant decreases of total cholesterol by -0.12 (95% CI: -0.21, -0.03) mmol/L, -4.64 (95% CI: -8.12, -1.16) mg/dL, p = 0.01 and increased HDL-cholesterol by 0.03 (95% CI: 0.00, 0.06) mmol/L, 1.15 (95% CI: 0.00, 1.93) mg/dL, p = 0.05, as well as in LDL-cholesterol -0.05 (95% CI: -0.11, 0.01) mmol/L, -1.93 (95% CI: -4.25, 0.39) mg/dL, p = 0.08 and triacylglycerols -0.07 (95% CI: -0.14, 0.00) mmol/L, -6.123 (95% CI: -12.25, 0.00) mg/dL, p = 0.06. Our results suggests that soy and its isoflavones can be effective in correction changes in lipid metabolism in postmenopausal women and may favorably influence in preventing cardiovascular events.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Lipídeos/sangue , Extratos Vegetais/administração & dosagem , Pós-Menopausa/sangue , Proteínas de Soja/administração & dosagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Isoflavonas/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
3.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445139

RESUMO

Recent evidence pinpoints extracellular vesicles (EVs) as key players in intercellular communication. Given the importance of cholesterol and sphingomyelin in EV biology, and the relevance of mitochondria-associated endoplasmic reticulum membranes (MAMs) in cholesterol/sphingomyelin homeostasis, we evaluated if MAMs and sphingomyelinases (SMases) could participate in ethanol-induced EV release. EVs were isolated from the extracellular medium of BV2 microglia treated or not with ethanol (50 and 100 mM). Radioactive metabolic tracers combined with thin layer chromatography were used as quantitative methods to assay phospholipid transfer, SMase activity and cholesterol uptake/esterification. Inhibitors of SMase (desipramine and GW4869) and MAM (cyclosporin A) activities were also utilized. Our data show that ethanol increases the secretion and inflammatory molecule concentration of EVs. Ethanol also upregulates MAM activity and alters lipid metabolism by increasing cholesterol uptake, cholesterol esterification and SMase activity in microglia. Notably, the inhibition of either SMase or MAM activity prevented the ethanol-induced increase in EV secretion. Collectively, these results strongly support a lipid-driven mechanism, specifically via SMases and MAM, to explain the effect of ethanol on EV secretion in glial cells.


Assuntos
Retículo Endoplasmático/efeitos dos fármacos , Etanol/farmacologia , Vesículas Extracelulares/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Esfingomielina Fosfodiesterase/metabolismo , Compostos de Anilina/farmacologia , Animais , Compostos de Benzilideno/farmacologia , Células Cultivadas , Colesterol/metabolismo , Ciclosporina/farmacologia , Retículo Endoplasmático/metabolismo , Vesículas Extracelulares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Fosfolipídeos/metabolismo
4.
Nutrients ; 13(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34371841

RESUMO

Excessive liver lipid deposition is a vital risk factor for the development of many diseases. Here, we fed Sprague-Dawley rats with a control or α-lipoic acid-supplemented diet (0.2%) for 5 weeks to elucidate the effects of α-lipoic acid on preventive ability, hepatic lipid metabolism-related gene expression, and the involved regulatory mechanisms. In the current study, α-lipoic acid supplementation lowered plasma triglyceride level and hepatic triglyceride content. Reduced hepatic lipid deposition was closely associated with inhibiting fatty acid-binding protein 1 and fatty acid synthase expression, as well as increasing phosphorylated hormone-sensitive lipase expression at the protein level in α-lipoic acid-exposed rats. Hepatic miRNA sequencing revealed increased expression of miR-3548 targeting the 3'untranslated region of Fasn mRNA, and the direct regulatory link between miRNA-3548 and FASN was verified by dual-luciferase reporter assay. Taken together, α-lipoic acid lowered hepatic lipid accumulation, which involved changes in miRNA-mediated lipogenic genes.


Assuntos
Suplementos Nutricionais , Ácido Graxo Sintase Tipo I/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , MicroRNAs/metabolismo , Ácido Tióctico/farmacologia , Animais , Ácido Graxo Sintases/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Expressão Gênica/efeitos dos fármacos , Lipogênese/genética , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
5.
Molecules ; 26(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34443619

RESUMO

This study was designed to investigate the influence of dietary chitosan feeding-duration on glucose and lipid metabolism in diabetic rats induced by streptozotocin and nicotinamide [a non-insulin-dependent diabetes mellitus (NIDDM) model]. Male Sprague-Dawley rats were used as experimental animals and divided into short-term (6 weeks) and long-term (11 weeks) feeding durations, and each duration contained five groups: (1) control, (2) control + 5% chitosan, (3) diabetes, (4) diabetes + 0.8 mg/kg rosiglitazone (a positive control), and (5) diabetes + 5% chitosan. Whether the chitosan feeding was for 6 or 11 weeks, the chitosan supplementation decreased blood glucose and lipids levels and liver lipid accumulation. However, chitosan supplementation decreased plasma tumor necrosis factor (TNF)-α, insulin levels, alanine aminotransferase (ALT) activity, insulin resistance (HOMA-IR), and adipose tissue lipoprotein lipase activity. Meanwhile, it increased plasma high-density lipoproteins (HDL)-cholesterol level, plasma angiopoietin-like-4 protein expression, and plasma triglyceride levels (at 11-week feeding duration only). Taken together, 11-week (long-term) chitosan feeding may help to ameliorate the glucose and lipid metabolism in a NIDDM diabetic rat model.


Assuntos
Quitosana/farmacologia , Diabetes Mellitus Experimental/metabolismo , Carboidratos da Dieta/farmacologia , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
6.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360852

RESUMO

Fluoxetine is an antidepressant commonly prescribed not only to adults but also to children for the treatment of depression, obsessive-compulsive disorder, and neurodevelopmental disorders. The adverse effects of the long-term treatment reported in some patients, especially in younger individuals, call for a detailed investigation of molecular alterations induced by fluoxetine treatment. Two-year fluoxetine administration to juvenile macaques revealed effects on impulsivity, sleep, social interaction, and peripheral metabolites. Here, we built upon this work by assessing residual effects of fluoxetine administration on the expression of genes and abundance of lipids and polar metabolites in the prelimbic cortex of 10 treated and 11 control macaques representing two monoamine oxidase A (MAOA) genotypes. Analysis of 8871 mRNA transcripts, 3608 lipids, and 1829 polar metabolites revealed substantial alterations of the brain lipid content, including significant abundance changes of 106 lipid features, accompanied by subtle changes in gene expression. Lipid alterations in the drug-treated animals were most evident for polyunsaturated fatty acids (PUFAs). A decrease in PUFAs levels was observed in all quantified lipid classes excluding sphingolipids, which do not usually contain PUFAs, suggesting systemic changes in fatty acid metabolism. Furthermore, the residual effect of the drug on lipid abundances was more pronounced in macaques carrying the MAOA-L genotype, mirroring reported behavioral effects of the treatment. We speculate that a decrease in PUFAs may be associated with adverse effects in depressive patients and could potentially account for the variation in individual response to fluoxetine in young people.


Assuntos
Antidepressivos/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Fluoxetina/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Animais , Ácidos Graxos Insaturados/metabolismo , Macaca mulatta , Masculino
7.
Nutrients ; 13(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200615

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is currently estimated as the most prevalent chronic liver disease in all age groups. An increasing body of evidence obtained in experimental and clinical data indicates that oxidative stress is the most important pathogenic factor in the development of NAFLD. The study aimed to investigate the impact of α-lipoic acid (LA), widely used as an antioxidant, on the effects of a hypercaloric choline-deficient diet. Male Wistar rats were divided into three groups: control diet (C); hypercaloric choline-deficient diet (HCCD), and hypercaloric choline-deficient diet with α-lipoic acid (HCCD+LA). Supplementation of HCCD with LA for eight weeks led to a decrease in visceral adipose tissue/body weight ratio, the activity of liver glutathione peroxidase and paraoxonase-1, plasma, and liver total antioxidant activity, as well as an increase in liver/body weight ratio, liver total lipid and triglyceride content, and liver transaminase activities compared to the HCCD group without LA. In conclusion, our study shows that α-lipoic acid detains obesity development but exacerbates the severity of diet-induced oxidative stress and lipid accumulation in the liver of male Wistar rats fed a hypercaloric choline-deficient diet.


Assuntos
Dieta , Comportamento Alimentar , Metabolismo dos Lipídeos , Fígado/patologia , Estresse Oxidativo , Ácido Tióctico/efeitos adversos , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Colina , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar
8.
Nutrients ; 13(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200816

RESUMO

The effectiveness of anthocyanins may differ according to their chemical structures; however, randomized clinical controlled trials (RCTs) or meta-analyses that examine the consequences of these structural differences have not been reported yet. In this meta-analysis, anthocyanins in test foods of 18 selected RCTs were categorized into three types: cyanidin-, delphinidin-, and malvidin-based. Delphinidin-based anthocyanins demonstrated significant effects on triglycerides (mean difference (MD): -0.24, p < 0.01), low-density lipoprotein cholesterol (LDL-C) (MD: -0.28, p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (MD: 0.11, p < 0.01), whereas no significant effects were observed for cyanidin- and malvidin-based anthocyanins. Although non-significant, favorable effects on total cholesterol (TC) and HDL-C were observed for cyanidin- and malvidin-based anthocyanins, respectively (both p < 0.1). The ascending order of effectiveness on TC and LDL-C was delphinidin-, cyanidin-, and malvidin-based anthocyanins, and the differences among the three groups were significant (both p < 0.05). We could not confirm the significant effects of each main anthocyanin on glucose metabolism; however, insulin resistance index changed positively and negatively with cyanidin- and delphinidin-based anthocyanins, respectively. Therefore, foods containing mainly unmethylated anthocyanins, especially with large numbers of OH groups, may improve glucose and lipid metabolism more effectively than those containing methylated anthocyanins.


Assuntos
Antocianinas/farmacologia , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Antocianinas/química , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Viés de Publicação , Risco
9.
Nutrients ; 13(6)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201166

RESUMO

Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.


Assuntos
Compostos Benzidrílicos/toxicidade , Feto/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Animais , Compostos Benzidrílicos/química , Receptor alfa de Estrogênio/metabolismo , Feminino , Feto/efeitos dos fármacos , Inflamação/patologia , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Fenóis/química , Gravidez , Ratos Sprague-Dawley
10.
Nutrients ; 13(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206655

RESUMO

Fish protein consumption exerts beneficial metabolic effects on human health, also correlating with a decreased risk for cardiovascular disease. Fish waste contains high amount of proteins and utilization may offer the opportunity for generating compounds advantageous for human health. Especially, fish waste protein hydrolysates beneficially influence pathways involved in body composition, exerting anti-inflammatory and antioxidant activities, making their potential supplementation in human disorders of increased interest. This study assessed the effect of a 10% (w/w) anchovy waste protein hydrolysate (APH) diet for 12 weeks in reducing atherosclerosis in ApoE-/- mice, through histological and immunohistochemical methods. In addition, monitoring of plaque development was performed, using high-frequency ultrasound and magnetic resonance imaging. Overall, the APH diet attenuated atherosclerotic plaque development, producing a regression of arterial lesions over time (p < 0.05). Twelve weeks on an APH diet had an anti-obesity effect, improving lipid metabolism and reducing hepatic enzyme activity. A significant reduction in plaque size and lipid content was observed in the aortic sinus of APH-fed mice, compared to the control (p < 0.001), whereas no differences in the extracellular matrix and macrophage recruitment were observed. Supplementation of APH significantly attenuates atherosclerosis in ApoE-/- mice, exerting a lipid-lowering activity. The opportunity to use fish waste protein hydrolysates as a nutraceutical in atherosclerosis is worthy of future investigations, representing a low cost, sustainable, and nutritional strategy with minimal environmental impact.


Assuntos
Aterosclerose/terapia , Suplementos Nutricionais , Proteínas de Peixes/farmacologia , Hipolipemiantes/farmacologia , Hidrolisados de Proteína/farmacologia , Animais , Fármacos Antiobesidade/farmacologia , Modelos Animais de Doenças , Fezes/química , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Placa Aterosclerótica/terapia , Alimentos Marinhos
11.
Molecules ; 26(12)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205604

RESUMO

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters.


Assuntos
Colesterol/sangue , Colesterol/metabolismo , Quercetina/farmacologia , Rutina/farmacologia , Administração Oral , Animais , Linhagem Celular Tumoral , Cricetinae , Flavonoides/farmacologia , Células Hep G2 , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Receptores X do Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Receptores de LDL/sangue , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos
12.
Biomed Pharmacother ; 139: 111665, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243607

RESUMO

Multicomponent herbal formulas (MCHFs) have earned a wide reputation for their definite efficacy in preventing or treating chronic complex diseases. However, holistic elucidation of the causal relationship between the bioavailable ingredients of MCHFs and their multitarget interactions is very challenging. To solve this problem, pharmacokinetics/pharmacometabolomics-pharmacodynamics (PK/PM-PD) combined with a multivariate biological correlation-network strategy was developed and applied to a classic MCHF, Baoyuan decoction (BYD), to clarify its active components and synergistic mechanism against cardiac hypertrophy (CH). First, multiple plasma metabolic biomarkers for ß-adrenergic agonist-induced CH rats were identified by using untargeted metabolomic profiling, and then, these CH-associated endogenous metabolites and the absorbed BYD-compounds in plasma at different treatment stages after oral administration of BYD were analyzed by using targeted PK and PM. Second, the dynamic relationship of BYD-related compounds and CH-associated endogenous metabolites and signaling pathways was built by using multivariate and bioinformatic correlation analysis. Finally, metabolic-related PD indicators were predicted and further verified by biological tests. The results demonstrated that the bioavailable BYD-compounds, such as saponins and flavonoids, presented differentiated and distinctive metabolic features and showed positive or negative correlations with various CH-altered metabolites and PD-indicators related to gut microbiota metabolism, amino acid metabolism, lipid metabolism, energy homeostasis, and oxidative stress at different treatment stages. This study provides a novel strategy for investigating the dynamic interaction between BYD and the biosystem, providing unique insight for disclosing the active components and synergistic mechanisms of BYD against CH, which also supplies a reference for other MCHF related research.


Assuntos
Cardiomegalia/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/farmacologia , Extratos Vegetais/farmacocinética , Aminoácidos/metabolismo , Animais , Biomarcadores/metabolismo , Cardiomegalia/metabolismo , Sinergismo Farmacológico , Flavonoides/farmacocinética , Flavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Saponinas/farmacocinética , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos
13.
Biomed Pharmacother ; 139: 111687, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243611

RESUMO

Obesity is one of the world's largest health problems, and 3-N-butylphthalide (NBP), a bioactive compound in celery, has been used in dieting and weight management programs. In this study, NBP prevented high-fat-diet-induced weight gain, reduced the food efficiency ratio, altered the blood biochemical profile, and reduced the obesity-related index. NBP reduced adiposity, white fat depots, liver weight, and hepatic steatosis in obese mice. NBP ameliorated the diabetic state by decreasing glucose levels and improving glucose and insulin tolerance. NBP increased uncoupling protein-1 expression in white adipose tissue and upregulated thermogenesis by enhancing mitochondrial respiration. NBP inhibited white adipocyte development by prohibiting lipid accumulation in human adipose-derived stem cells. NBP increased free fatty acid uptake and the oxygen consumption rate in beige adipocytes. Our results suggest that NBP could be used as functional natural supplement against obesity and its associated disorders.


Assuntos
Benzofuranos/farmacologia , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/fisiologia , Obesidade/metabolismo , Substâncias Protetoras/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Células Cultivadas , Fígado Gorduroso/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Termogênese/efeitos dos fármacos
14.
Nutrients ; 13(7)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202167

RESUMO

In a recent study, we showed that konjac glucomannan (KGM) inhibits rice gruel-induced postprandial increases in plasma glucose and insulin levels. To extend this research, we investigated the effects of KGM addition to rice gruel on pre- and postprandial concentrations of circulating lipoprotein lipase (LPL), glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), hepatic triglyceride lipase (HTGL), free fatty acids (FFA), and triglycerides (TG). A total of 13 Japanese men, without diabetes, dyslipidemia, or gastrointestinal diseases, interchangeably ingested rice gruel containing no KGM (0%G), rice gruel supplemented with 0.4% KGM (0.4%G), and rice gruel supplemented with 0.8% KGM (0.8%G), every Sunday for 3 weeks. Blood samples were obtained at baseline and at 30, 60, and 120 min after ingestion to measure the abovementioned lipid parameters. Lipid parameters showed small, but significant, changes. Significant reductions were found in circulating FFA levels among all participants. Circulating TG levels significantly declined at 30 min and then remained nearly constant in the 0.8%G group but exhibited no significant difference in the 0%G and 0.4%G groups. Although circulating levels of LPL and GPIHBP1 significantly decreased in the 0%G and 0.4%G groups, they increased at 120 min in the 0.8%G group. Participants in the 0%G and 0.4%G groups showed significant decreases in circulating HTGL levels, which was not observed in the 0.8%G group. Our results demonstrate the novel pleiotropic effects of KGM. Supplementation of rice gruel with KGM powder led to TG reduction accompanied by LPL and GPIHBP1 elevation and HTGL stabilization, thereby attenuating TG metabolism.


Assuntos
Suplementos Nutricionais , Grão Comestível , Mananas , Oryza , Triglicerídeos/sangue , Adulto , Estudos Cross-Over , Método Duplo-Cego , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipase Lipoproteica/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial/efeitos dos fármacos , Pós , Receptores de Lipoproteínas/sangue
15.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208952

RESUMO

As sphingolipids are constituents of the cell and vacuole membranes of eukaryotic cells, they are a critical component acquired from our daily diets. In the present review, we highlight the knowledge regarding how dietary sphingolipids affect our health, particularly our intestinal health. Animal- and plant-derived foods contain, respectively, sphingomyelin (SM) and glucosylceramide (GlcCer) as their representative sphingolipids, and the sphingoid base as a specific structure of sphingolipids also differs depending upon the source and class. For example, sphingosine is predominant among animal sphingolipids, and tri-hydroxy bases are present in free ceramide (Cer) from plants and fungi. Dietary sphingolipids exhibit low absorption ratios; however, they possess various functions. GlcCer facilitates improvements in intestinal impairments, lipid metabolisms, and skin disorders, and SM can exert both similar and different effects compared to those elicited by GlcCer. We discuss the digestion, absorption, metabolism, and function of sphingolipids while focused on the structure. Additionally, we also review old and new classes in the context of current advancements in analytical instruments.


Assuntos
Intestinos/fisiologia , Plantas/química , Esfingolipídeos/farmacologia , Animais , Estilo de Vida Saudável , Humanos , Intestinos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Esfingolipídeos/farmacocinética
16.
Toxicology ; 458: 152850, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34217793

RESUMO

Micro and nanoplastics are one of the major emerging environmental contaminants. Their impact on human health is less explored. There are several in vitro studies on their cellular uptake and accumulation, where micro and nanoplastics were mostly reported to be non-cytotoxic. The effects caused by the direct contact of nanoplastics with the immune system, especially at the cellular level is less known. Here we report that RAW 264.7 macrophages undergo differentiation into lipid laden foam cells when exposed to polystyrene nanoplastics (50 µg/mL). We found that exposure of RAW 264.7 macrophages to sulfate-modified polystyrene nanoplastics results in the accumulation of lipid droplets in the cytoplasm leading to foam cell formation. Exposure to high concentration of polystyrene nanoplastics (100 and 200 µg/mL) results in increased reactive oxygen species and impair lysosomes in macrophages. The exposure of BV2 microglial cells to polystyrene nanoplastics (50 µg/mL) induces lipid accumulation. In addition, our results indicate the role of polystyrene nanoplastics in altering the lipid metabolism in murine macrophages in vitro. In the present study we reported that polystyrene nanoplastics stabilized with anionic surfactants can be potent stimuli for lipotoxicity and foam cell formation leading to the pathogenesis of atherosclerosis posing major threat for animal and human health.


Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/metabolismo , Microplásticos/toxicidade , Nanopartículas/toxicidade , Poliestirenos/toxicidade , Animais , Aterosclerose/induzido quimicamente , Proliferação de Células/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Células Espumosas/efeitos dos fármacos , Hemólise , Imunidade Celular/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Células RAW 264.7 , Espécies Reativas de Oxigênio , Tensoativos
17.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299301

RESUMO

Metformin can reduce cardiovascular risk independent of glycemic control. The mechanisms behind its non-glycemic benefits, which include decreased energy intake, lower blood pressure and improved lipid and fatty acid metabolism, are not fully understood. In our study, metformin treatment reduced myocardial accumulation of neutral lipids-triglycerides, cholesteryl esters and the lipotoxic intermediates-diacylglycerols and lysophosphatidylcholines in a prediabetic rat model (p < 0.001). We observed an association between decreased gene expression and SCD-1 activity (p < 0.05). In addition, metformin markedly improved phospholipid fatty acid composition in the myocardium, represented by decreased SFA profiles and increased n3-PUFA profiles. Known for its cardioprotective and anti-inflammatory properties, metformin also had positive effects on arachidonic acid metabolism and CYP-derived arachidonic acid metabolites. We also found an association between increased gene expression of the cardiac isoform CYP2c with increased 14,15-EET (p < 0.05) and markedly reduced 20-HETE (p < 0.001) in the myocardium. Based on these results, we conclude that metformin treatment reduces the lipogenic enzyme SCD-1 and the accumulation of the lipotoxic intermediates diacylglycerols and lysophosphatidylcholine. Increased CYP2c gene expression and beneficial effects on CYP-derived arachidonic acid metabolites in the myocardium can also be involved in cardioprotective effect of metformin.


Assuntos
Ácido Araquidônico/metabolismo , Metformina/farmacologia , Miocárdio/metabolismo , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/metabolismo , Animais , Metabolismo Basal/efeitos dos fármacos , Biomarcadores/sangue , Cardiotônicos/farmacologia , Modelos Animais de Doenças , Ácidos Graxos Dessaturases/metabolismo , Coração/efeitos dos fármacos , Hiperlipoproteinemia Tipo IV/tratamento farmacológico , Hiperlipoproteinemia Tipo IV/metabolismo , Hipoglicemiantes/farmacologia , Mediadores da Inflamação/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Fatores de Risco
18.
Ecotoxicol Environ Saf ; 221: 112464, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34198189

RESUMO

Antibiotics are widely used in the treatment of bacterial infections and as food additives in the livestock industry. The wide usage of antibiotics causes residues in animal products, like milk, eggs and meat. A number of studies have reported that antibiotic residues exist at high concentrations in watercourses around the world. Doxycycline (DH), oxytetracycline (OTCC) and florfenicol (FF) are the three most commonly used veterinary antibiotics in China. However, studies of the toxic effects of DH, OTCC and FF are limited. In this study, six-moth-old healthy male adult zebrafish were exposed to 0, 10, 30, 100 µg/L DH, OTCC or FF for 21 days. After exposure, some biochemical parameters changed significantly, including total cholesterol (TC), triglyceride (TG), pyruvate and acid phosphatase (ACP). In addition, mucus secretion in the gut decreased and the transcription of related genes also decreased significantly. Moreover, the composition of microbiota in the gut changed significantly. DH, OTCC and FF exposure caused the decrease of diversity of gut microbiota. The relative abundance of Proteobacteria increased significantly after OTCC and FF exposure and Fusobacteria decreased in all antibiotic-treated groups. Further functional prediction analysis also suggested changes in gut microbiota in the OTCC and FF-treated groups, especially those linked to metabolism. To support this idea, we confirmed that some glycolipid related genes also increased significantly in the liver of adult zebrafish after antibiotic exposure. According to these results, DH, OTCC or FF exposure could cause the gut microbiota dysbiosis and dysfunction, and hepatic metabolic disorder in adult male zebrafish.


Assuntos
Antibacterianos/toxicidade , Doxiciclina/toxicidade , Disbiose/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Oxitetraciclina/toxicidade , Tianfenicol/análogos & derivados , Animais , Disbiose/metabolismo , Microbioma Gastrointestinal/genética , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Tianfenicol/toxicidade , Peixe-Zebra/microbiologia
19.
Molecules ; 26(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200517

RESUMO

Epoxy-α-lapachone (Lap) and Epoxymethyl-lawsone (Law) are oxiranes derived from Lapachol and have been shown to be promising drugs for Leishmaniases treatment. Although, it is known the action spectrum of both compounds affect the Leishmania spp. multiplication, there are gaps in the molecular binding details of target enzymes related to the parasite's physiology. Molecular docking assays simulations were performed using DockThor server to predict the preferred orientation of both compounds to form stable complexes with key enzymes of metabolic pathway, electron transport chain, and lipids metabolism of Leishmania spp. This study showed the hit rates of both compounds interacting with lanosterol C-14 demethylase (-8.4 kcal/mol to -7.4 kcal/mol), cytochrome c (-10.2 kcal/mol to -8.8 kcal/mol), and glyceraldehyde-3-phosphate dehydrogenase (-8.5 kcal/mol to -7.5 kcal/mol) according to Leishmania spp. and assessed compounds. The set of molecular evidence reinforces the potential of both compounds as multi-target drugs for interrupt the network interactions between parasite enzymes, which can lead to a better efficacy of drugs for the treatment of leishmaniases.


Assuntos
Leishmania/efeitos dos fármacos , Naftoquinonas/farmacologia , Simulação por Computador , Citocromos c/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Compostos de Epóxi/farmacologia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Leishmaniose/tratamento farmacológico , Leishmaniose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Simulação de Acoplamento Molecular
20.
Biomed Pharmacother ; 138: 111532, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311531

RESUMO

Fufang Zhenzhu Tiaozhi formula (FTZ), a preparation of Chinese herbal medicine, has various pharmacological properties, such as hypoglycemic, hypolipidemic, anticoagulant, and anti-inflammatory activities. Hepatocyte apoptosis is a marker of nonalcoholic steatohepatitis (NASH) and contributes to liver injury, fibrosis, and inflammation. Given the multiple effects of FTZ, we investigated whether FTZ can be a therapeutic agent for NASH and its mechanism. In the present study, we observed that FTZ treatment had an obviously favorable influence on hepatic steatosis and fibrosis in the histopathologic features of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) with NASH minipigs. In addition, immunohistochemical analysis showed increased expression of the fibrotic marker α-smooth muscle actin (α-SMA), and a TUNEL assay revealed increased apoptotic positive hepatic cells in the liver tissues of the model group. Furthermore, FTZ administration reduced the increased expression of α-SMA, and FTZ inhibited apoptosis by affecting Bcl-2/Bax and cleaved caspase-3 expression. Mechanistically, our data suggested that FTZ treatment attenuated hepatic steatosis and fibrosis via the adenosine monophosphate-activated protein kinase (AMPK) pathway. In vitro studies showed that FTZ also attenuated intracellular lipid accumulation in HepG2 cells exposed to palmitic acid (PA) and oleic acid (OA). FTZ upregulated the expression levels of P-AMPK and BCL-2 and downregulated BAX. The changes induced by FTZ were reversed by Compound C, an inhibitor of AMPK. In conclusion, FTZ attenuated NASH by ameliorating steatosis and hepatocyte apoptosis, which is attributable to the regulation of the AMPK pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Doença das Coronárias/enzimologia , Doença das Coronárias/etiologia , Doença das Coronárias/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/enzimologia , Células Hep G2 , Humanos , Lipídeos/sangue , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/enzimologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Suínos , Porco Miniatura
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