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1.
Arch Endocrinol Metab ; 63(4): 427-437, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365625

RESUMO

OBJECTIVE: Chronic kidney disease (CKD) risk is inconsistent in the normal-weight, overweight, and obese individuals due to the heterogeneity of metabolic status. This meta-analysis aimed to examine the combined effects of body mass index (BMI) and metabolic status on CKD risk. MATERIALS AND METHODS: The MEDLINE, EMBASE, and Web of Knowledge databases were systematically searched up to March 2019 to identify all eligible studies investigating the CKD risk (defined as GFR < 60 mL/min per 1.73 m2 and/or microalbuminuria or proteinuria) associated with the body size phenotypes which are known as metabolically unhealthy normal-weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO). The classification of subjects in included studies as metabolically unhealthy was based on the presence of three components of metabolic syndrome. BMI categorization was based on the criteria of included studies. The risk estimates and 95% confidence intervals (CIs) were extracted and pooled using random effects analysis. RESULTS: A total of 9 prospective cohort studies with 128773 participants and 4797 incident cases were included in the meta-analysis. Compared with healthy normal-weight individuals as reference, MUNW and MHO subjects showed an increased risk for CKD events with a pooled RR of 1.58 (95% CI = 1.28-1.96) in MUNW and 1.55 (95% CI = 1.34-1.79) in MHO persons. Also, MHOW was at increased risk for CKD (RR = 1.34, 95% CI = 1.20-1.51). MUHO individuals were at the highest risk for the development of CKD (RR = 2.13, 95% CI = 1.66-2.72). CONCLUSIONS: Individuals with metabolic abnormality, although at normal-weight, have an increased risk for CKD. Healthy overweight and obese individuals had higher risk; refuting the notion that metabolically healthy overweight and obese phenotypes are benign conditions.


Assuntos
Peso Corporal/genética , Síndrome Metabólica/genética , Fenótipo , Insuficiência Renal Crônica/genética , Índice de Massa Corporal , Humanos , Síndrome Metabólica/metabolismo , Estudos Observacionais como Assunto , Insuficiência Renal Crônica/metabolismo , Risco
2.
Sci Total Environ ; 689: 149-159, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271984

RESUMO

Numerous studies suggest that amphibians are highly sensitive to endocrine disruptors (ED) but their precise role in population decline remains unknown. This study shows that frogs exposed to a mixture of ED throughout their life cycle, at environmentally relevant concentrations, developed an unexpected metabolic syndrome. Female Silurana (Xenopus) tropicalis exposed to a mixture of benzo[a]pyrene and triclosan (50 ng·L-1 each) from the tadpole stage developed liver steatosis and transcriptomic signature associated with glucose intolerance syndrome, and pancreatic insulin hyper secretion typical of pre-diabetes. These metabolic disorders were associated with delayed metamorphosis and developmental mortality in their progeny, both of which have been linked to reduced adult recruitment and reproductive success. Indeed, F1 females were smaller and lighter and presented reduced reproductive capacities, demonstrating a reduced fitness of ED-exposed Xenopus. Our results confirm that amphibians are highly sensitive to ED even at concentrations considered to be safe for other animals. This study demonstrates that ED might be considered as direct contributing factors to amphibian population decline, due to their disruption of energetic metabolism.


Assuntos
Benzo(a)pireno/toxicidade , Disruptores Endócrinos/toxicidade , Doenças Metabólicas/veterinária , Metamorfose Biológica/efeitos dos fármacos , Triclosan/toxicidade , Xenopus/metabolismo , Animais , Relação Dose-Resposta a Droga , Feminino , Fígado/efeitos dos fármacos , Fígado/fisiologia , Fígado/fisiopatologia , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/metabolismo , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/metabolismo , Síndrome Metabólica/veterinária , Reprodução/efeitos dos fármacos , Transcriptoma
3.
Nat Commun ; 10(1): 2375, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147543

RESUMO

Human antigen R (HuR) is a member of the Hu family of RNA-binding proteins and is involved in many physiological processes. Obesity, as a worldwide healthcare problem, has attracted more and more attention. To investigate the role of adipose HuR, we generate adipose-specific HuR knockout (HuRAKO) mice. As compared with control mice, HuRAKO mice show obesity when induced with a high-fat diet, along with insulin resistance, glucose intolerance, hypercholesterolemia and increased inflammation in adipose tissue. The obesity of HuRAKO mice is attributed to adipocyte hypertrophy in white adipose tissue due to decreased expression of adipose triglyceride lipase (ATGL). HuR positively regulates ATGL expression by promoting the mRNA stability and translation of ATGL. Consistently, the expression of HuR in adipose tissue is reduced in obese humans. This study suggests that adipose HuR may be a critical regulator of ATGL expression and lipolysis and thereby controls obesity and metabolic syndrome.


Assuntos
Tecido Adiposo Branco/metabolismo , Proteína Semelhante a ELAV 1/genética , Intolerância à Glucose/genética , Hipercolesterolemia/genética , Resistência à Insulina/genética , Lipase/genética , Obesidade/genética , Adipócitos/patologia , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/imunologia , Animais , Crescimento Celular , Dieta Hiperlipídica , Proteína Semelhante a ELAV 1/metabolismo , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Intolerância à Glucose/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Hipertrofia , Inflamação/imunologia , Lipase/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Biossíntese de Proteínas , Estabilidade de RNA/genética , Gordura Subcutânea/metabolismo
4.
Methods Mol Biol ; 2018: 269-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31228162

RESUMO

Metabolic syndrome is a complex disorder that comprises several other complex disorders, including obesity, hypertension, dyslipidemia, and diabetes. There are several rat models that encompass component features of MetS. Some models are inbred strains selected for one or more traits underlying MetS; others are population models with genetic risk for MetS traits, are induced by environmental stressors such as diet, are spontaneous monogenic mutant models, or are congenic strains derived from a combination of these models. Together they can be studied to identify the genetic and physiological underpinnings of MetS to identify candidate genes or mechanisms for study in human MetS subjects.


Assuntos
Modelos Animais de Doenças , Síndrome Metabólica/etiologia , Animais , Colesterol/metabolismo , Predisposição Genética para Doença , Lipoproteínas HDL/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Ratos , Ratos Endogâmicos
5.
J Physiol Pharmacol ; 70(1)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31172973

RESUMO

Obesity is characterised by imbalance in lipid metabolism manifested by high concentrations of circulating triacylglycerols and total cholesterol as well as low high-density lipoprotein (HDL) levels. Abnormalities related to these lipids lead to metabolic complications such as type 2 diabetes, arterial hypertension and cardiovascular disease. Despite extensive research, it is still unclear why a subset of obese subjects develop metabolic syndrome, while others do not. The aim of our work was to assess total and plasma membrane expressions of cholesterol transport proteins: adipocyte ATP-binding cassette A1 (ABCA1), adipocyte ATP-binding cassette G1 (ABCG1), class B scavenger receptor (SR-BI) in visceral and subcutaneous adipose tissue of obese subjects with and without metabolic syndrome. To keep our preliminary study group uniform, we focused on women, who constitute the majority of bariatric patients. The study was performed on 34 patients: 24 morbidly obese women subjected to bariatric surgery, half of whom had metabolic syndrome; and 10 lean subjects undergoing elective laparoscopic cholecystectomy. Total and plasma membrane expressions of cholesterol transport proteins (SR-BI, ABCA1 and ABCG1) were assessed in samples of both visceral and subcutaneous adipose and analysed in relation to other clinical and laboratory parameters. We demonstrated lower plasma membrane expressions of ABCG1 in visceral adipose tissue of obese patients with metabolic syndrome as compared to lean ones. In addition, total ABCG1 expressions in both types of adipose tissue were lower in morbidly obese patients with metabolic syndrome compared to those without metabolic syndrome. Plasma membrane ABCA1 expressions in visceral adipose tissue were lower in the group of morbidly obese patients without metabolic syndrome, compared to lean patients. We did not find any significant differences in SR-BI expressions. Because of ABCG1 is responsible for cholesterol efflux to HDL, reduced plasma membrane expression of ABCG1 in VAT of morbidly obese women with metabolic syndrome may leads to a significantly decreased concentration of HDL in serum. This may be also confirmed by high positive correlation between both parameters.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Tecido Adiposo/metabolismo , Síndrome Metabólica/metabolismo , Obesidade Mórbida/metabolismo , Adulto , Idoso , Colesterol/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Hipertensão/metabolismo , Pessoa de Meia-Idade , Receptores Depuradores Classe B/metabolismo , Adulto Jovem
6.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 46(2): 51-56, abr.-jun. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-183388

RESUMO

Antecedentes y objetivo: En la posmenopausia se presentan alteraciones en el metabolismo de los lípidos, sensibilidad a la insulina e incremento del tejido adiposo visceral, lo que se asocia a un aumento del riesgo cardiometabólico. La osteocalcina (OCN) es una proteína de remodelación ósea, que recientemente se ha observado que participa en la regulación del metabolismo de la glucosa, lípidos y del tejido adiposo. Son limitados los estudios de OCN en la etapa posmenopáusica. El objetivo de este trabajo fue investigar la relación de la concentración de OCN con la obesidad y el síndrome metabólico (SM) en mujeres pre y posmenopáusicas. Métodos: Estudio transversal que incluyó a 261 participantes de 45 a 60 años, quienes fueron evaluadas clínicamente y se les midió glucosa y perfil de lípidos. La OCN sérica y la insulina se determinaron por quimioluminiscencia. Resultados: De las participantes, 128 fueron premenopáusicas y 133 posmenopáusicas; el 33% de las participantes presentaban SM. En las mujeres posmenopáusicas, la concentración de OCN fue superior en comparación a las premenopáusicas (7,2±4,0 vs. 5,5±6,4 ng/mL, p<0,019). La concentración de OCN en la mujer posmenopáusica con SM fue más elevada en comparación al grupo control (8,4±5,1 vs. 6,3±2,8 ng/mL, p=0,003). Conclusión: En la posmenopausia, el déficit de estrógenos y la resistencia a la insulina se asocian a un incremento de la concentración de OCN


Introduction and objective: Changes in lipid metabolism, insulin sensitivity, and visceral adipose tissue increase cardio-metabolic risk. Recent evidence suggests that osteocalcin (OCN) may play a role in metabolism. However, little is known about the OCN in post-menopausal women. The aim of this study was to investigate the relationship between the concentration of OCN with obesity and metabolic syndrome (MS) in pre-and post-menopausal women. Methods: A cross-sectional study was conducted that included 261 participants who were reviewed clinically and underwent laboratory studies, including the determination of serum OCN and insulin by chemiluminescence. Results: Of the participants, 128 were pre-menopausal, 133 post-menopausal, and 33% had MS. OCN concentration was higher in post-menopausal women than in pre-menopausal (7.7±5.7 vs. 5.3 + 2.6 ng/mL, P<.001). OCN levels in post-menopausal women with MS were greater than those without MS (8.4±5.1 vs 6.3±2.8 ng/mL, P.003). Conclusion: Oestrogen deficiency and insulin resistance are associated with increased OCN during the stage of post-menopausal stage


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Osteocalcina/sangue , Síndrome Metabólica/sangue , Obesidade/sangue , Resistência à Insulina , Síndrome Metabólica/metabolismo , Síndrome Metabólica/etiologia , Obesidade/complicações , Estudos Transversais , Osteocalcina/metabolismo , Pós-Menopausa/metabolismo
7.
BMC Complement Altern Med ; 19(1): 97, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060549

RESUMO

BACKGROUND: Endothelial dysfunction (ED) has been observed in individuals with metabolic syndrome (MetS) and contributes to the initiation and progression of atherosclerosis. The primary management of MetS involves lifestyle modifications and treatment of its individual components with drugs all of which have side effects. Thus, it would be of advantageous if natural products would be used as adjuncts or substitutes for conventional drugs. The aim of the present study was to evaluate the effect of standardized aqueous extract of fruits of Phyllanthus emblica (P. emblica) 250 mg and 500 mg twice daily on ED, oxidative stress, systemic inflammation and lipid profile in subjects with MetS. METHODS: In this randomised, double-blind, placebo-controlled clinical study endothelial function was measured by calculating reflection index (RI) using digital plethysmograph. Oxidative stress biomarkers used were nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA). Systemic inflammation was measured by determining high sensitivity C-reactive protein (hsCRP) and dyslipidemia by lipid profile. ANOVA, paired and unpaired t-test were used. P-value < 0.05 was considered statistically significant. RESULTS: Out of 65 screened subjects all 59 enrolled completed the study. P. emblica aqueous extract (PEE), 250 mg and 500 mg twice daily dosing, showed significant reduction in mean RI, measure of endothelial function, at 8 and 12 weeks (p <  0.001) compared to baseline and placebo. Significant mean % change was seen in oxidative stress biomarkers, NO (+ 41.89%, + 50.7%), GSH (+ 24.31%, + 53.22%) and MDA (- 21.02%, - 31.44%), and systemic inflammation biomarker, hsCRP (- 39.68%, - 53.77%) (p <  0.001) at 12 weeks with 250 mg and 500 mg twice daily dosage respectively. Significant mean % change was also seen at 12 weeks with TC (- 7.71%, - 11.11%), HDL-C (+ 7.33% + 22.16%, p <  0.05), LDL-C (- 11.39%, - 21.8%) and TG (- 9.81%, - 19.22%) respectively with 250 mg and 500 mg twice daily (p <  0.001). PEE 500 mg twice daily was significantly more efficacious than the 250 mg twice daily and placebo. No participant discontinued the study because of adverse events. CONCLUSIONS: P.emblica aqueous extract significantly improved endothelial function, oxidative stress, systemic inflammation and lipid profile at both dosages tested, but especially at 500 mg twice daily. Thus, this product may be used as an adjunct to conventional therapy (lifestyle modification and pharmacological intervention) in the management of metabolic syndrome. TRIAL REGISTRATION: This study was registered with Clinical Trials Registry - India (CTRI) with the registration number of CTRI/2017/09/009606 . The study was registered retrospectively on 4th September 2017.


Assuntos
Inflamação/tratamento farmacológico , Lipídeos/sangue , Síndrome Metabólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Phyllanthus emblica , Extratos Vegetais , Idoso , Método Duplo-Cego , Dislipidemias/metabolismo , Feminino , Frutas/química , Glutationa/sangue , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
8.
Muscle Nerve ; 60(2): 124-136, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31074875

RESUMO

Complementary and alternative treatment modalities are commonly utilized by patients for neuropathy and neuropathic pain due to perceived lack of benefit from conventional medical treatment. As the association between metabolic syndrome and neuropathy is increasingly recognized, diet and lifestyle interventions are becoming important components in the management of neuropathy. Progress in the understanding of the gut-immune interaction highlights the role the gut microbiome and inflammation plays in the modulation of neuropathy and neuropathic pain. Evidence for nutritional interventions, exercise, supplements, acupuncture, and mindfulness-based practices in the treatment of neuropathic pain is encouraging. This article reviews the available evidence to support the safe use of complementary and alternative treatments for commonly encountered conditions associated with neuropathy and neuropathic pain. Muscle Nerve 60: 124-136, 2019.


Assuntos
Dietoterapia , Suplementos Nutricionais , Terapia por Exercício , Estilo de Vida , Neuralgia/terapia , Doenças do Sistema Nervoso Periférico/terapia , Complexo Vitamínico B/uso terapêutico , Acetilcarnitina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Curcumina/uso terapêutico , Dieta , Disbiose/metabolismo , Exercício , Ácidos Graxos Ômega-3/uso terapêutico , Ácido Fólico/análogos & derivados , Ácido Fólico/uso terapêutico , Microbioma Gastrointestinal , Humanos , Medicina Integrativa , Síndrome Metabólica/metabolismo , Neuralgia/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Fosfato de Piridoxal/uso terapêutico , Ácido Tióctico/uso terapêutico , Vitamina B 12/análogos & derivados , Vitamina B 12/uso terapêutico , Complexo Vitamínico B/metabolismo , Deficiência de Vitaminas do Complexo B , Vitamina D/uso terapêutico
9.
Biomed Res Int ; 2019: 8748253, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080832

RESUMO

Aging is related to a number of functional and morphological changes leading to progressive decline of the biological functions of an organism. Reactive Oxygen Species (ROS), released by several endogenous and exogenous processes, may cause important oxidative damage to DNA, proteins, and lipids, leading to important cellular dysfunctions. The imbalance between ROS production and antioxidant defenses brings to oxidative stress conditions and, related to accumulation of ROS, aging-associated diseases. The purpose of this review is to provide an overview of the most relevant data reported in literature on the natural compounds, mainly phytochemicals, with antioxidant activity and their potential protective effects on age-related diseases such as metabolic syndrome, diabetes, cardiovascular disease, cancer, neurodegenerative disease, and chronic inflammation, and possibly lower side effects, when compared to other drugs.


Assuntos
Envelhecimento/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Envelhecimento/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Humanos , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
10.
Heart Fail Clin ; 15(3): 349-358, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31079693

RESUMO

The interplay between metabolic syndrome (MetS) and heart failure (HF) is intricate. Population studies show that MetS confers an increased risk to develop HF and this effect is mediated by insulin resistance (IR). However, obesity, a key component in MetS and common partner of IR, is protective in patients with established HF, although IR confers an increased risk of dying by HF. Such phenomenon, known as "obesity paradox," accounts for the complexity of the HF-MetS relationship. Because IR impacts more on outcomes than MetS itself, the former may be considered the actual target for MetS in HF patients.


Assuntos
Insuficiência Cardíaca/etiologia , Resistência à Insulina/fisiologia , Síndrome Metabólica/complicações , Saúde Global , Insuficiência Cardíaca/epidemiologia , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Morbidade/tendências , Prognóstico , Fatores de Risco , Taxa de Sobrevida/tendências
11.
Int J Mol Sci ; 20(9)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31035722

RESUMO

Childhood obesity represents an important public health issue worldwide and is strongly linked to metabolic alterations such as hypertension, insulin resistance, and dyslipidemia. The constellation of these conditions is commonly known as Metabolic Syndrome (MetS). Metabolic syndrome is not just a simple cluster of metabolic complications due to excess of adipose tissue, but is considered a risk factor for cardiovascular diseases. Evidence from several human and animal studies suggests that environmental and nutritional exposure during pregnancy may affect the newborn development and future health through epigenetic changes, playing a potential role in determining obesity and obesity-related complications. Understanding how nutritional epigenetic mechanisms contribute to the "transgenerational risk" for obesity and metabolic dysfunction is crucial in order to develop early prevention strategies for children's health. Nutrigenetics is the science that studies the role of nutrients in gene expression. Long Chain Polyunsaturated Fatty Acids (LCPUFAs) are known for their health benefits, especially in relation to their ability to modulate inflammation and improve some obesity-associated comorbidities, mainly by decreasing plasma triglycerides. Recent nutrigenetic research is focusing on the potential role of LCPUFAs in influencing epigenetic markers. In this review, we present the most recent updates about the possible interaction between n-3 LCPUFAs and epigenetic pathways in metabolic syndrome. Literature from MEDLINE® and the Cochrane database between May 2005 and December 2018 has been scanned.


Assuntos
Epigênese Genética , Ácidos Graxos Ômega-3/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Acetilação , Fatores Etários , Animais , Biomarcadores , Suscetibilidade a Doenças , Retículo Endoplasmático/metabolismo , Histonas/metabolismo , Humanos , Redes e Vias Metabólicas , Peroxissomos/metabolismo , DNA Metiltransferases Sítio Específica (Adenina-Específica)
12.
Oxid Med Cell Longev ; 2019: 1724194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049126

RESUMO

Cardiovascular diseases (CVD) constitute one of the most prevalent health problems worldwide, being strongly associated with metabolic syndrome (MS). Oxidative stress (OS) is present in both CVD and MS. Infusions of Hibiscus sabdariffa Linnaeus (HSL) have antioxidant properties and could therefore decrease the presence of OS in these diseases. The aim of this study was to evaluate myocardial protection during ischemia/reperfusion due to the antioxidant effect of HSL infusion (3%) on a MS rat model induced by the administration of 30% sucrose in drinking water. We determined in control, MS, and MS + HSL rat hearts (n = 6 per group) cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and activities of manganese and copper/zinc superoxide dismutases (Mn and Cu/Zn-SOD), peroxidases, glutathione peroxidase (GPx), catalase (CAT), glutathione s-transferase (GST), glutathione reductase (GR), and glutathione (GSH). We also determined lipoperoxidation (LPO), total antioxidant capacity (TAC), and the nitrate/nitrite ratio (NO3 -/NO2 -). The treatment with the HSL infusion restored the CMP (p = 0.01) and CVR (p = 0.04) and increased the Mn- (p = 0.02), Cu/Zn-SOD (p = 0.05), peroxidases (p = 0.04), GST (p = 0.02) activity, GHS (p = 0.02), TAC (p = 0.04), and NO3 -/NO2 - (p = 0.01) and decreased the LPO (p = 0.02) in the heart of MS rats undergoing ischemia/reperfusion. The results suggest that the treatment with an infusion from HSL calices protects the cardiac function from damage by ischemia and reperfusion through the antioxidant activities of the substances it possesses. It favors antioxidant enzymatic activities and nonenzymatic antioxidant capacity.


Assuntos
Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Hibiscus/química , Síndrome Metabólica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Cardiotônicos/química , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Proteínas Musculares/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Ratos
13.
Cell Mol Life Sci ; 76(13): 2547-2557, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30968170

RESUMO

Emerging evidence shows that palmitic acid (PA), a common fatty acid in the human diet, serves as a signaling molecule regulating the progression and development of many diseases at the molecular level. In this review, we focus on its regulatory roles in the development of five pathological conditions, namely, metabolic syndrome, cardiovascular diseases, cancer, neurodegenerative diseases, and inflammation. We summarize the clinical and epidemiological studies; and also the mechanistic studies which have identified the molecular targets for PA in these pathological conditions. Activation or inactivation of these molecular targets by PA controls disease development. Therefore, identifying the specific targets and signaling pathways that are regulated by PA can give us a better understanding of how these diseases develop for the design of effective targeted therapeutics.


Assuntos
Autofagia , Doenças Cardiovasculares/patologia , Inflamação/patologia , Síndrome Metabólica/patologia , Neoplasias/patologia , Doenças Neurodegenerativas/patologia , Ácido Palmítico/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Humanos , Inflamação/metabolismo , Síndrome Metabólica/metabolismo , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Transdução de Sinais
14.
Int J Mol Sci ; 20(7)2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30959940

RESUMO

Fatty acid (FA) profiles in the plasma of patients with metabolic syndrome and chronic kidney disease (CKD) seem to be identical despite their different etiology (dietary mistakes vs. cachexia). The aim of this study was to compare both profiles and to highlight the differences that could influence the improvement of the treatment of patients in both groups. The study involved 73 women, including 24 patients with chronic kidney disease treated with haemodialysis, 19 patients with metabolic syndrome (MetS), and 30 healthy women in the control group. A total of 35 fatty acids and derivatives were identified and quantified by gas chromatography. Intensified elongation processes from acid C10:0 to C16:0 were noted in both groups (more intense in MetS), as well as an increased synthesis of arachidonic acid (C20:4n6), which was more intense in CKD. Significant correlations of oleic acid (C18:1n9), gamma linoleic acid (C18:3n6), and docosatetraenoate acid (C22:4n6) with parameters of CKD patients were observed. In the MetS group, auxiliary metabolic pathways of oleic acid were activated, which simultaneously inhibited the synthesis of eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) from alpha lipoic acid (ALA). On the other hand, in the group of female patients with CKD, the synthesis of EPA and DHA was intensified. Activation of the synthesis of oleic acid (C18: 1n9 ct) and trans-vaccinic acid (C18:1) is a protective mechanism in kidney diseases and especially in MetS due to the increased concentration of saturated fatty acid (SFA) in plasma. The cause of the increased amount of all FAs in plasma in the CKD group, especially in the case of palmitic (C16:0) and derivatives stearic (C18:0) acids, may be the decomposition of adipose tissue and the progressing devastation of the organism, whereas, in the MetS group, dietary intake seems to be the main reason for the increase in SFA. Moreover, in MetS, auxiliary metabolic pathways are activated for oleic acid, which cause the simultaneous inhibition of EPA and DHA synthesis from ALA, whereas, in the CKD group, we observe an increased synthesis of EPA and DHA. The higher increase of nervonic acid (C24:1) in CKD suggests a higher degree of demyelination and loss of axons.


Assuntos
Ácidos Graxos/metabolismo , Síndrome Metabólica/metabolismo , Insuficiência Renal Crônica/metabolismo , Ácido Araquidônico/metabolismo , Cromatografia Gasosa , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Ácidos Graxos Monoinsaturados/metabolismo , Feminino , Humanos , Ácido Oleico/metabolismo
15.
Molecules ; 24(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987086

RESUMO

Mixtures of resveratrol (RSV) + quercetin (QRC) have antioxidant properties that probably impact on fatty liver in metabolic syndrome (MS) individuals. Here, we study the effects of a mixture of RSV + QRC on oxidative stress (OS) and fatty liver in a rat model of MS. Weanling male Wistar rats were separated into four groups (n = 8): MS rats with 30% sucrose in drinking water plus RSV + QRC (50 and 0.95 mg/kg/day, respectively), MS rats without treatment, control rats (C), and C rats plus RSV + QRC. MS rats had increased systolic blood pressure, triglycerides, insulin levels, insulin resistance index homeostasis model (HOMA), adiponectin, and leptin. The RSV + QRC mixture compensated these variables to C values (p < 0.01) in MS rats. Lipid peroxidation and carbonylation were increased in MS. Total antioxidant capacity and glutathione (GSH) were decreased in MS and compensated in MS plus RVS + QRC rats. Catalase, superoxide dismutase isoforms, peroxidases, glutathione-S-transferase, glutathione reductase, and the expression of Nrf2 were decreased in MS and reversed in MS plus RVS + QRC rats (p < 0.01). In conclusion, the mixture of RSV + QRC has benefic effects on OS in fatty liver in the MS rats through the improvement of the antioxidant capacity and by the over-expression of the master factor Nrf2, which increases the antioxidant enzymes and GSH recycling.


Assuntos
Antioxidantes/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Quercetina/administração & dosagem , Resveratrol/administração & dosagem , Animais , Biomarcadores , Modelos Animais de Doenças , Fígado Gorduroso/sangue , Fígado Gorduroso/prevenção & controle , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Síndrome Metabólica/sangue , Estresse Oxidativo/efeitos dos fármacos , Ratos
17.
Int J Mol Sci ; 20(9)2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31027340

RESUMO

Insulin-resistance is one of the main factors responsible for the onset and progression of Metabolic Syndrome (MetS). Among all polyphenols, the effects of flavonoids and their main food sources on insulin sensitivity have been widely evaluated in molecular and clinical studies. The aim of this review is to analyse the data observed in vitro, in vivo and in clinical trials concerning the effects of flavonoids on insulin resistance and to determine the molecular mechanisms with which flavonoids interact with insulin signaling.


Assuntos
Flavonoides/metabolismo , Resistência à Insulina/fisiologia , Animais , Ensaios Clínicos como Assunto , Humanos , Síndrome Metabólica/metabolismo
18.
Environ Int ; 127: 664-670, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30991222

RESUMO

OBJECTIVES: To assess whether exposure to specific classes of neuroactive non-organochlorine insecticides is associated with diabetes mellitus or related metabolic traits. METHODS: Eligibility criteria: Any type of epidemiological and human exposure studies providing an exposure contrast to neuroactive non-organochlorine insecticides and a measure of association to diabetes mellitus or related metabolic traits. We will include published peer-reviewed studies in both English and non-English language. INFORMATION SOURCES: Articles will be located in the NCBI PubMed, Embase, Scopus, Web of Science and LILACS databases, supplemented with manual searching of reference lists and articles citing the included studies. Risk of bias assessment: Risk of bias in individual studies will be assessed using tools from the Navigation Guide systematic review methodology, while the risk of bias at the outcome level will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. Data synthesis and analysis: When studies are sufficiently similar in population, exposure, comparator and effect estimate to meaningfully allow quantitative synthesis, we will perform meta-analysis. Otherwise, results will be summarized qualitatively. FUNDING: The authors are paid employees of their respective institutions. MRHH is a Ph.D. student working under grants from Aarhus University and the National Research Centre for the Working Environment. REGISTRATION: PROSPERO CRD42017068861.


Assuntos
Diabetes Mellitus , Inseticidas/farmacologia , Humanos , Síndrome Metabólica/metabolismo , Projetos de Pesquisa
19.
Vet J ; 244: 51-59, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30825895

RESUMO

The main objective of this study was to identify analytes that could change and that could help to clarify the metabolic and physiopathological changes related to canine obesity-related metabolic dysfunction (ORMD). For this, serum from 35 overweight/obese dogs, with and without ORMD, was submitted to a comprehensive panel of biochemistry analysis, a gel-free tandem mass tag isobaric label-based proteomic analysis, and, finally, selected proteins were used as a starting point for creating a protein interaction network. Dogs with ORMD showed significantly higher serum concentrations of alanine aminotransferase (ALT), alkaline phosphatase (ALP), Ca, total proteins, albumin, total cholesterol, triglycerides, glucose, and butyrylcholinesterase (BChE) activity in comparison with dogs without ORMD. Proteomic analysis revealed that 23 proteins related to lipid metabolism, the complement factor system, cellular adhesion and functionality, inflammation, and coagulation were altered in dogs with ORMD. Finally, the obtained protein interaction network highlighted that the central term of this network was the negative regulation of the immune response. These data suggest that canine ORMD is associated with changes in analytes that reflect altered lipid metabolism, and liver and immune function impairment and suggests the potential for a prothrombotic state and lung function alterations.


Assuntos
Doenças do Cão/metabolismo , Síndrome Metabólica/veterinária , Obesidade/veterinária , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Glicemia , Colesterol/sangue , Doenças do Cão/sangue , Cães , Feminino , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Obesidade/complicações , Triglicerídeos/sangue
20.
Chem Pharm Bull (Tokyo) ; 67(3): 199-202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30827999

RESUMO

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor superfamily and include three subtypes (PPARα, PPARδ, and PPARγ). They regulate gene expression in a ligand-dependent manner. PPARα plays an important role in lipid metabolism. PPARγ is involved in glucose metabolism and is a potential therapeutic target in Type 2 diabetes. PPARδ ligands are candidates for the treatment of metabolic disorders. Thus, the detection of PPAR ligands may facilitate the treatment of various diseases. In this study, to identify PPAR ligands, we engineered reporter cell lines that can be used to quantify PPARγ and PPARδ activity. We evaluated several known ligands using these reporter cell lines and confirmed that they are useful for PPAR ligand detection. Furthermore, we evaluated extracts of approximately 200 natural resources and found various extracts that enhance reporter gene activity. Finally, we identified a main alkaloid of the Evodia fruit, evodiamine, as a PPARγ activator using this screening tool. These results suggest that the established reporter cell lines may serve as a useful cell-based screening tool for finding PPAR ligands to ameliorate metabolic syndromes.


Assuntos
Síndrome Metabólica/prevenção & controle , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Linhagem Celular , Ensaios de Triagem em Larga Escala , Humanos , Ligantes , Síndrome Metabólica/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Extratos Vegetais/farmacologia
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