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1.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361774

RESUMO

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.


Assuntos
Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Composição de Medicamentos/métodos , Hipertensão/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Polifenóis/farmacologia , Elementos de Resposta Antioxidante , Antioxidantes/química , Antioxidantes/farmacocinética , Arginina/análogos & derivados , Arginina/antagonistas & inibidores , Arginina/metabolismo , Cardiotônicos/química , Cardiotônicos/farmacocinética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Portadores de Fármacos , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Dislipidemias/metabolismo , Dislipidemias/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/química , Polifenóis/farmacocinética , Transdução de Sinais
2.
Molecules ; 26(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207498

RESUMO

Cardiovascular diseases (CVDs) are a global health burden that greatly impact patient quality of life and account for a huge number of deaths worldwide. Despite current therapies, several side effects have been reported that compromise patient adherence; thus, affecting therapeutic benefits. In this context, plant metabolites, namely volatile extracts and compounds, have emerged as promising therapeutic agents. Indeed, these compounds, in addition to having beneficial bioactivities, are generally more amenable and present less side effects, allowing better patient tolerance. The present review is an updated compilation of the studies carried out in the last 20 years on the beneficial potential of essential oils, and their compounds, against major risk factors of CVDs. Overall, these metabolites show beneficial potential through a direct effect on these risk factors, namely hypertension, dyslipidemia and diabetes, or by acting on related targets, or exerting general cellular protection. In general, monoterpenic compounds are the most studied regarding hypotensive and anti-dyslipidemic/antidiabetic properties, whereas phenylpropanoids are very effective at avoiding platelet aggregation. Despite the number of studies performed, clinical trials are sparse and several aspects related to essential oil's features, namely volatility and chemical variability, need to be considered in order to guarantee their efficacy in a clinical setting.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Óleos Voláteis/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Dislipidemias/complicações , Dislipidemias/metabolismo , Dislipidemias/patologia , Humanos , Óleos Voláteis/química , Estresse Oxidativo , Qualidade de Vida , Fatores de Risco
3.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298929

RESUMO

Dyslipidemia is characterized by increasing plasma levels of low-density lipoprotein-cholesterol (LDL-C), triglycerides (TGs) and TG-rich lipoproteins (TGRLs) and is a major risk factor for the development of atherosclerotic cardiovascular disorders (ASCVDs). It is important to understand the metabolic mechanisms underlying dyslipidemia to develop effective strategies against ASCVDs. Angiopoietin-like 3 (ANGPTL3), a member of the angiopoietin-like protein family exclusively synthesized in the liver, has been demonstrated to be a critical regulator of lipoprotein metabolism to inhibit lipoprotein lipase (LPL) activity. Genetic, biochemical, and clinical studies in animals and humans have shown that loss of function, inactivation, or downregulated expression of ANGPTL3 is associated with an obvious reduction in plasma levels of TGs, LDL-C, and high-density lipoprotein-cholesterol (HDL-C), atherosclerotic lesions, and the risk of cardiovascular events. Therefore, ANGPTL3 is considered an alternative target for lipid-lowering therapy. Emerging studies have focused on ANGPTL3 inhibition via antisense oligonucleotides (ASOs) and monoclonal antibody-based therapies, which have been carried out in mouse or monkey models and in human clinical studies for the management of dyslipidemia and ASCVDs. This review will summarize the current literature on the important role of ANGPTL3 in controlling lipoprotein metabolism and dyslipidemia, with an emphasis on anti-ANGPTL3 therapies as a potential strategy for the treatment of dyslipidemia and ASCVDs.


Assuntos
Proteínas Semelhantes a Angiopoietina/metabolismo , Dislipidemias/metabolismo , Lipoproteínas/metabolismo , Animais , Aterosclerose/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol , Humanos , Triglicerídeos/metabolismo
4.
Toxicol Appl Pharmacol ; 426: 115644, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34252412

RESUMO

Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor α (hPPARα)-expressing mice fed an American diet. Mice were exposed to PFOA (3.5 mg/L) in drinking water for 6 weeks resulting in a serum concentration of 48 ± 9 µg/ml. In male and female hPPARα mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of PPARα alone also increased total liver TG, and PFOA treatment had little effect on liver TG in PPARα null mice. In hPPARα mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Intriguingly, in female PPARα null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPARα-dependent manner, but not in adipose. The results of our study and others reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.


Assuntos
Caprilatos/toxicidade , Dieta Ocidental , Dislipidemias/induzido quimicamente , Fluorcarbonetos/toxicidade , Fígado/efeitos dos fármacos , PPAR alfa/genética , Animais , Peso Corporal/efeitos dos fármacos , Dislipidemias/genética , Dislipidemias/metabolismo , Dislipidemias/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Genótipo , Lipidômica , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Transgênicos , Tamanho do Órgão/efeitos dos fármacos , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Estados Unidos
5.
Nutrients ; 13(6)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204055

RESUMO

Lately, matcha green tea has gained popularity as a beverage and food additive. It has proved to be effective in preventing obesity and related metabolic syndromes. However, the underlying mechanisms of its control effects against non-alcoholic fatty liver disease (NAFLD) are complicated and remain elusive. In the present study, we performed an in vivo experiment using male C57BL/6 mice fed with a high-fat diet and simultaneously treated with matcha for six weeks. Serum biochemical parameters, histological changes, lipid accumulation, inflammatory cytokines, and relevant indicators were examined. Dietary supplementation of matcha effectively prevented excessive accumulation of visceral and hepatic lipid, elevated blood glucose, dyslipidemia, abnormal liver function, and steatosis hepatitis. RNA sequencing analyses of differentially expressed genes in liver samples indicated that matcha treatment decreased the activity of lipid droplet-associated proteins and increased the activity of cytochrome P450 enzymes, suggesting improved metabolic capacity and liver function. The current study provided evidence for new dietary strategies based on matcha supplementation to ameliorate lipotoxicity-induced obesity and NALFD.


Assuntos
Antioxidantes/administração & dosagem , Metabolismo dos Lipídeos/fisiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/terapia , Chá , Animais , Glicemia/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Dislipidemias/metabolismo , Inflamação , Fígado/metabolismo , Testes de Função Hepática , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/etiologia
6.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203309

RESUMO

The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid ß-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.


Assuntos
Aterosclerose/metabolismo , Doenças Cardiovasculares/metabolismo , Dislipidemias/metabolismo , Fígado/metabolismo , Animais , Humanos , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia
7.
Nat Commun ; 12(1): 3505, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108472

RESUMO

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.


Assuntos
Diabetes Mellitus Tipo 2/genética , Dislipidemias/genética , Predisposição Genética para Doença/genética , Adulto , Variação Biológica da População , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dislipidemias/metabolismo , Exoma/genética , Genótipo , Humanos , Herança Multifatorial , Penetrância , Medição de Risco
8.
Biomolecules ; 11(6)2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070757

RESUMO

Cardiovascular disorders are leading mortality causes worldwide, often with a latent evolution. Vascular health depends on endothelial function, arterial stiffness, and the presence of atherosclerotic plaques. Preventive medicine deserves special attention, focusing on modifiable cardiovascular risk factors, including diet. A diet rich in fruits and vegetables has well-known health benefits, especially due to its polyphenolic components. Anthocyanins, water-soluble flavonoid species, responsible for the red-blue color in plants and commonly found in berries, exert favorable effects on the endothelial function, oxidative stress, inhibit COX-1, and COX-2 enzymes, exert antiatherogenic, antihypertensive, antiglycation, antithrombotic, and anti-inflammatory activity, ameliorate dyslipidemia and arterial stiffness. The present review aims to give a current overview of the mechanisms involved in the vascular protective effect of anthocyanins from the human diet, considering epidemiological data, in vitro and in vivo preclinical research, clinical observational, retrospective, intervention and randomized studies, dietary and biomarker studies, and discussing preventive benefits of anthocyanins and future research directions.


Assuntos
Antocianinas/uso terapêutico , Aterosclerose/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Endotélio Vascular/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Placa Aterosclerótica/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Antocianinas/química , Antocianinas/metabolismo , Aterosclerose/metabolismo , Aterosclerose/mortalidade , Dislipidemias/metabolismo , Dislipidemias/mortalidade , Humanos , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/mortalidade
9.
J Steroid Biochem Mol Biol ; 212: 105940, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34119628

RESUMO

Due to the biochemical importance of cholesterol homeostasis in cardiovascular disease (CVD), this study was aimed to identify metabolic signatures of serum sterols according to atherosclerotic CVD severity. Biogically active free cholesterol and its 11 analogues in serum samples obtained from subjects who underwent cardiovascular intervention were quantitatively evaluated by gas chromatography-mass spectrometry (GCMS). Study groups were divided by 29 patients with stable angina (SA), 35 patients with acute coronary syndrome (ACS), and 41 controls. In all subjects, serum levels of cholesterol and its upstream precursors of 7-dehydrocholesterol, lathosterol, and lanosterol were closely associated with CVD risk factors, such as total cholesterol, low-density lipoprotein cholesterol (LDL-C), and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio (r = 0.407 ∼ 0.684, P < 0.03 for all). Metabolic ratios of lathosterol/cholesterol (control = 55.75 ± 34.34, SA = 51.04 ± 34.93, ACS = 36.52 ± 22.00; P < 0.03) and lanosterol/cholesterol (control = 12.27 ± 7.43, SA = 10.97 ± 9.13, ACS = 8.01 ± 5.82; P < 0.03), were remarkably decreased. Both metabolic ratios and individual concentrations of lathosterol and lanosterol were also decreased in subjects with statin treatment than those in the control group without statin treatment (P < 0.05 for all), whereas three metabolic ratios of dietary sterols (sitosterol, campesterol, and stigmasterol) to free cholesterol were increased after statin therapy (P < 0.05 for all) in both SA and ACS groups. The present metabolic signatures suggest that both lathosterol/cholesterol and lanosterol/cholesterol ratios corresponding to cholesterol biosynthesis may reflect statin response. Individual dietary sterols to cholesterol ratios resulted in higher intestinal cholesterol absorption after statin therapy.


Assuntos
Doença da Artéria Coronariana/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Esteróis/biossíntese , Absorção Fisiológica , Adulto , Idoso , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/cirurgia , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Dislipidemias/cirurgia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Esteróis/sangue
10.
Biomed Res Int ; 2021: 6687551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104650

RESUMO

In the present study, we examined the synergetic effect of forskolin and mevastatin administration on lipid profile and lipid metabolism in omental adipose tissue in dyslipidemic rats. The study was conducted on forty male albino rats. The rats were randomly classified into four main groups of ten animals in each group as follows: group A, served as control nontreated; group B, rats that received Triton WR 1339 (500 mg/kg); group C, rats that received Triton WR 1339 with forskolin (100% FSK extract 0.5 mg/kg/day) for four weeks; and group D, dyslipidemic rats received both mevastatin and forskolin. At the end of the experimental period, blood and omental adipose tissue samples were collected, preserved, and used for biochemical determination of lipid profile and mRNA expression profile of adenylate cyclase (AC), hormone-sensitive lipase, respectively (HSL), and adenosine monophosphate-activated protein kinase (AMPK). The results showed a significant decline in the serum concentration of total cholesterol, LDL-cholesterol, and triglycerides, although there was a significant increase in serum levels of HDL-cholesterol and glycerol in rats received forskolin alone or with mevastatin when compared with control and dyslipidemic groups. The mRNA expression levels of AC, HSL, and AMPK were significantly increased in omental adipose tissue of rats received forskolin when compared with other groups. In conclusion, forskolin acts synergistically with mevastatin to lower lipid profile and improve lipid metabolism in dyslipidemic rats through upregulation of AMPK expression.


Assuntos
Monofosfato de Adenosina/metabolismo , Colforsina/farmacologia , Dislipidemias/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/fisiologia , Lovastatina/análogos & derivados , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , HDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lovastatina/farmacologia , Masculino , Ratos , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos
11.
Ecotoxicol Environ Saf ; 219: 112350, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34022626

RESUMO

Arsenic trioxide (ATO) has been known as common environmental pollution, and is deemed to a threat to global public health. Curcumin (Cur) is a phytoconstituent, which has been demonstrated to have antioxidant effects. In the current experiment, we investigated the efficacy of Cur against ATO-induced kidney injury and explored the potential molecular mechanisms that have not yet been fully elucidated in ducks. The results showed that treatment with Cur attenuated ATO-induced body weight loss, reduced the content of ATO in the kidney, and improved ATO-induced kidney pathological damage. Cur also remarkably alleviated the ascent of ATO-induced MDA level and activated the Nrf2 pathway. Using the TEM, we found Cur relieved mitochondrial swelling, autolysosomes generating and nuclear damage. Simultaneously, Cur was found that it not only significantly reduced autophagy-related mRNA and protein levels (mTOR, LC3-Ⅰ, LC3-Ⅱ, Atg-5, Beclin1, Pink1 and Parkin) and but also decreased apoptosis-related mRNA and protein expression levels (cleaved caspase-3, Cytc, p53 and Bax). Furthermore, through nontargeted metabolomics analysis, we observed that lipid metabolism balance was disordered by ATO exposure, while Cur administration alleviated the disturbance of lipid metabolism. These results showed ATO could induce autophagy and apoptosis by overproducing ROS in the kidney of ducks, and Cur might relieve excessive autophagy, apoptosis and disturbance of lipid metabolism by regulating oxidative stress. Collectively, our findings explicate the potential therapeutic value of Cur as a new strategy to a variety of disorders caused by ATO exposure.


Assuntos
Trióxido de Arsênio/toxicidade , Curcumina/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Patos/metabolismo , Dislipidemias/metabolismo , Rim/efeitos dos fármacos , Nefropatias/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Serina-Treonina Quinases TOR
12.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926097

RESUMO

Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (p ˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (p ˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (p ˂ 0.05) and decreased CYP4A (p ˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (p ˂ 0.01), lipogenesis (p ˂ 0.05) and lipolysis (p ˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal period.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Transtornos do Metabolismo dos Lipídeos/etiologia , Metabolismo dos Lipídeos/fisiologia , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/fisiologia , Dieta Hiperlipídica , Dislipidemias/metabolismo , Fígado Gorduroso/metabolismo , Feminino , Glucose/metabolismo , Insulina/metabolismo , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Transtornos do Metabolismo dos Lipídeos/fisiopatologia , Lipídeos/sangue , Lipogênese/efeitos dos fármacos , Lipólise , Fígado/metabolismo , Menopausa/metabolismo , Menopausa/fisiologia , Obesidade/metabolismo , Ovariectomia/efeitos adversos , Pós-Menopausa/metabolismo , Pós-Menopausa/fisiologia , Ratos , Ratos Wistar , Triglicerídeos/metabolismo , Ganho de Peso
13.
Molecules ; 26(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804179

RESUMO

Amomum tsao-ko Crevost et Lemaire (Zingiberaceae) is a medicinal herb found in Southeast Asia that is used for the treatment of malaria, abdominal pain, dyspepsia, etc. The aim of this study was to investigate the effect of an ethanol extract of Amomum tsao-ko (EAT) on obesity and hyperlipidemia in C57BL/6 mice fed a high-carbohydrate diet (HCD). First, the mice were divided into five groups (n = 6/group) as follows: normal diet, HCD, and HCD+EAT (100, 200, and 400 mg/kg/day), which were orally administered with EAT daily for 84 days. Using microcomputed tomography (micro-CT) analysis, we found that EAT inhibited not only body-weight gain, but also visceral fat and subcutaneous fat accumulation. Histological analysis confirmed that EAT decreased the size of fat tissues. EAT consistently improved various indices, including plasma levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein, high-density lipoprotein, atherogenic index, and cardiac risk factors, which are related to dyslipidemia-a major risk factor for heart disease. The contents of TC and TG, as well as the lipid droplets of HCD-induced hepatic accumulation in the liver tissue, were suppressed by EAT. Taken together, these findings suggest the possibility of developing EAT as a therapeutic agent for improving HCD-induced obesity and hyperlipidemia.


Assuntos
Amomum/química , Carboidratos/efeitos adversos , Dislipidemias/tratamento farmacológico , Obesidade/tratamento farmacológico , Plantas Medicinais/química , Zingiberaceae/química , Tecido Adiposo/efeitos dos fármacos , Animais , Dieta/efeitos adversos , Dislipidemias/metabolismo , Lipoproteínas LDL/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Triglicerídeos/metabolismo
14.
Cell Biochem Funct ; 39(5): 646-657, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33720434

RESUMO

This study investigated whether swimming protocol induces adaptations to sex-specific oxidative stress and Nrf2/Keap-1 pathway in the liver of mice fed a high-calorie diet (HCD) during the early life period. Male and female Swiss mice were fed a standard or high-calorie (enriched with 20% lard and 20% corn syrup) diets, and the trained mice were subjected to a swimming protocol (5 days/week) from 21st to 49th postnatal days. Males fed a HCD had more pronounced alterations in all parameters evaluated than females. Although there was no increase in body weight, the fat deposition was higher in male mice exposed to diet. The intake of HCD induced dyslipidemia mainly in males. In a sex-dependent manner, the hepatic markers of oxidative damage, antioxidant defences, and a sensitive sulfhydryl protein were altered in mice fed a HCD. Swimming counteracted dyslipidemia, hepatic oxidative stress, and the Nrf2/Keap-1 signalling downregulation, in a sex-dependent manner, in mice exposed to a HCD. These findings demonstrate that a non-pharmacological therapy, swimming protocol, contributed to adaptations of sex-specific hepatic oxidative stress and Nrf2/Keap-1 regulation in male mice fed a HCD.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Dislipidemias/induzido quimicamente , Fígado Gorduroso/induzido quimicamente , Proteína 1 Associada a ECH Semelhante a Kelch/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Animais , Regulação para Baixo/efeitos dos fármacos , Dislipidemias/metabolismo , Fígado Gorduroso/metabolismo , Feminino , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fatores Sexuais , Natação
15.
PLoS One ; 16(3): e0246184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730037

RESUMO

Macaíba palm seed kernel is a source of lipids and phenolic compounds. The objective of this study was to evaluate the effects of macaíba palm seed kernel on anxiety, memory, and oxidative stress in the brain of health and dyslipidemic rats. Forty rats were used, divided into 4 groups (n = 10 each): control (CONT), dyslipidemic (DG), kernel (KG), and Dyslipidemic kernel (DKG). Dyslipidemia was induced using a high fat emulsion for 14 days before treatment. KG and DKG received 1000 mg/kg of macaíba palm seed kernel per gavage for 28 days. After treatment, anxiety tests were carried out using the Open Field Test (OFT), Elevated Plus Maze (EPM), and the Object Recognition Test (ORT) to assess memory. In the animals' brain tissue, levels of malondialdehyde (MDA) and total glutathione (GSH) were quantified to determine oxidative stress. The data were treated with Two Way ANOVA followed by Tukey (p <0.05). Results demonstrated that the animals treated with kernel realized more rearing. DG and KG groomed less compared with CONT and DKG compared with all groups in OFT. KG spent more time in aversive open arms compared with CONT and DKG compared with all groups in EPM. Only DKG spent more time in the central area in EMP. KG and DKG showed a reduction in the exploration rate and MDA values (p <0.05). Data showed that macaíba palm seed kernel consumption induced anxiolytic-like behaviour and decreased lipids peroxidation in rats' brains. On the other hand, this consumption by healthy and dyslipidemic animals compromises memory.


Assuntos
Arecaceae/química , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dislipidemias/metabolismo , Memória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Encéfalo/fisiopatologia , Dislipidemias/tratamento farmacológico , Dislipidemias/fisiopatologia , Dislipidemias/psicologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Sementes/química
16.
Int Immunopharmacol ; 95: 107340, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33667999

RESUMO

Obesity is an important factor implicated in chronic kidney disease (CKD). Juglanin (Jug) is a natural compound extracted from the crude Polygonumaviculare, showing anti-inflammatory and anti-diabetic effects. However, whether Jug has protective effects against obesity-induced renal injury, little has been investigated. Herein, we attempted to explore the potential of Jug in mediating obesity-induced kidney disease in high fat diet (HFD)-challenged mice. Our results suggested that chronic HFD feeding markedly increased the body weights of mice compared to the ones fed with normal chow diet (NCD), along with significant glucose intolerance and insulin resistance. However, these metabolic disorders induced by HFD were effectively alleviated by Jug treatments in a dose-dependent manner. Moreover, HFD-challenged mice showed apparent histopathological changes in renal tissues with significant collagen accumulation, which were attenuated by Jug supplementation. In addition, Jug treatment decreased the expression levels of kidney injury molecule-1 (KIM-1), while increased nephrin and podocin expression levels in kidney of HFD-challenged mice, improving the renal dysfunction. Furthermore, HFD led to lipid deposition in kidney samples of mice by enhancing abnormal lipid metabolism. In addition, HFD promoted the releases of circulating pro-inflammatory cytokines, and enhanced the renal inflammation by activating nuclear factor-kappa B/histone deacetylase 3 (NF-κB/HDAC3) signaling. HFD-induced dyslipidemia and inflammation were considerably abrogated by Jug administration in mice. The protective effects of Jug against renal injury were confirmed in palmitate (PA)-stimulated HK2 cells in vitro mainly through suppressing the nuclear translocation of NF-κB and HDAC3, repressing inflammation and lipid accumulation eventually. Hence, Jug could ameliorate HFD-induced kidney injury mainly through blocking the NF-κB/HDAC3 nuclear translocation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dislipidemias/tratamento farmacológico , Glicosídeos/uso terapêutico , Hipolipemiantes/uso terapêutico , Quempferóis/uso terapêutico , Nefropatias/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dieta Hiperlipídica , Dislipidemias/metabolismo , Dislipidemias/patologia , Glicosídeos/farmacologia , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Hipolipemiantes/farmacologia , Resistência à Insulina , Quempferóis/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Sci Rep ; 11(1): 6013, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727609

RESUMO

Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of cognitive dysfunction. We previously showed that patients with metabolic syndrome (MetS) had significantly higher plasma levels of electronegative very-low-density lipoprotein (VLDL) than did healthy controls. However, the effects of electronegative-VLDL on the brain and cognitive function remain unclear. In this study, VLDL isolated from healthy volunteers (nVLDL) or patients with MetS (metVLDL) was administered to mice by means of tail vein injection. Cognitive function was assessed by using the Y maze test, and plasma and brain tissues were analyzed. We found that mice injected with metVLDL but not nVLDL exhibited significant hippocampus CA3 neuronal cell loss and cognitive dysfunction. In mice injected with nVLDL, we observed mild glial cell activation in the medial prefrontal cortex (mPFC) and hippocampus CA3. However, in mice injected with metVLDL, plasma and brain TNF-α and Aß-42 levels and glial cell activation in the mPFC and whole hippocampus were higher than those in control mice. In conclusion, long-term exposure to metVLDL induced levels of TNF-α, Aß-42, and glial cells in the brain, contributing to the progression of cognitive dysfunction. Our findings suggest that electronegative-VLDL levels may represent a new therapeutic target for cognitive dysfunction.


Assuntos
Região CA3 Hipocampal , Disfunção Cognitiva , Lipoproteínas VLDL/toxicidade , Córtex Pré-Frontal , Animais , Região CA3 Hipocampal/metabolismo , Região CA3 Hipocampal/patologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Dislipidemias/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Lipoproteínas VLDL/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Camundongos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia
18.
Sci Rep ; 11(1): 6115, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731756

RESUMO

Several studies have shown that probiotics and synbiotics ameliorate dyslipidemia. However, the molecular mechanisms mediating their effects remain to be determined. Therefore, we aimed to compare the effects of a probiotic, a prebiotic, and a synbiotic in dyslipidemic Sprague-Dawley rats, and explore the mechanisms involved using a proteomic approach. The rats were allocated to five groups: a control group that was fed normal chow, and four high-fat diet-fed groups, three of which were administered a probiotic (Lactobacillus acidophilus), a prebiotic (inulin), or a combination of the two (a synbiotic) for 30 days. We showed that the administration of inulin, and especially L. acidophilus, improved the lipid profile and reduced the serum concentrations of inflammatory markers in high-fat diet-fed rats. Proteomic analysis showed changes in lipid elongation, glycerolipid metabolism, activation of antioxidants, and a reduction in the activation of the mitogen-activated protein kinase signaling pathway in the livers of rats administered L. acidophilus, which likely mediate its beneficial effects on inflammation and dyslipidemia by reduced the levels of 18.56% CRP, 35.71% TNF-α 25.6% LDL-C and 28.57% LDL-C/HDL-C ratio when compared to HF group. L. acidophilus and inulin may represent effective natural means of maintaining inflammation and dyslipidemia.


Assuntos
Dieta Hiperlipídica , Dislipidemias/dietoterapia , Inulina/farmacologia , Lactobacillus acidophilus , Prebióticos , Probióticos/farmacologia , Animais , Dislipidemias/metabolismo , Ratos , Ratos Sprague-Dawley
19.
Int J Mol Sci ; 22(4)2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33562440

RESUMO

Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases. This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Colesterol/metabolismo , Transportador 1 de Cassete de Ligação de ATP/deficiência , Transportador 1 de Cassete de Ligação de ATP/genética , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Doenças Transmissíveis/etiologia , Doença das Coronárias/etiologia , Diabetes Mellitus Tipo 2/etiologia , Dislipidemias/etiologia , Dislipidemias/metabolismo , Oftalmopatias/etiologia , Variação Genética , Humanos , Resistência à Insulina , Lipídeos/sangue , Hepatopatias/etiologia , Malária/etiologia , MicroRNAs/genética , Modelos Biológicos , Mutação , Neoplasias/etiologia , Doenças do Sistema Nervoso/etiologia , Doença de Tangier/etiologia
20.
Biochem Genet ; 59(3): 781-798, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33543406

RESUMO

Increasing burden of non-communicable diseases like diabetes and cardiovascular disorders has made the global health scenario more challenging. Dyslipidemia in diabetes is a compounding risk factor for cardiovascular diseases, but there is dearth of identifying appropriate signatures to address this issue. The protein, adiponectin, is actively involved in regulating glucose levels as well as fatty acid breakdown playing crucial role in dyslipidemia and vascular complications. To identify the underlying genetic and molecular profile of adiponectin metabolic pathway in diabetic dyslipidemia and to correlate it with known biochemical and oxidative stress parameters of T2DM, we performed a case-control study in a total 264 individuals belonging to three categories such as diabetes with dyslipidemia (n = 88), diabetes without dyslipidemia (n = 86) and normal healthy controls (n = 90). Expression of adiponectin (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) were measured in visceral and subcutaneous adipose tissues. A significant downregulated expression of ADIPOQ and its receptors in adipose tissues and PBMCs were linked with diabetic dyslipidemic condition. A multiple linear regression followed by MDR analysis implicated the elevated plasma malondialdehyde and decreased adiponectin level to be correlated with diabetic dyslipidemia. More interestingly, two single nucleotide polymorphisms of ADIPOQ (rs2241766 and rs1501299) were genetically associated with the risk of developing dyslipidemia. Other important biochemical factors found to be increased in diabetic dyslipidemic conditions included plasma C-reactive protein and 4-hydroxynonenal adducts. Our results explore, a complex interplay of genetic and biochemical parameters in diabetic dyslipidemia which is significant from the perspective of risk stratification and novel therapeutic strategy development.


Assuntos
Adiponectina/genética , Diabetes Mellitus Tipo 2/genética , Dislipidemias/metabolismo , Peroxidação de Lipídeos , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Dislipidemias/complicações , Dislipidemias/genética , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade
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