Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 442
Filtrar
1.
Int J Mol Sci ; 21(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218354

RESUMO

Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. By inhibiting enzymatic decomposition, DPP-4 inhibitors increase the half-life of incretins such as GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitors polypeptide) and prolong their action. Some studies present results suggesting the anti-sclerotic and vasculoprotective effects of vildagliptin reaching beyond glycemic control. Vildagliptin is able to limit inflammation by suppression of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway and proinflammatory agents such as TNF-α (tumor necrosis factor α), IL-1ß (Interleukin-1ß), and IL-8 (Interleukin 8). Moreover, vildagliptin regulates lipid metabolism; attenuates postprandial hypertriglyceridemia; and lowers serum triglycerides, apolipoprotein B, and blood total cholesterol levels. This DPP-4 inhibitor also reduces macrophage foam cell formation, which plays a key role in atheromatous plaque formation and stability. Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. By affecting the endothelium, inflammation, and lipid metabolism, vildagliptin may affect the development of atherosclerosis at its various stages. The article presents a summary of the studies assessing vasculoprotective effects of vildagliptin with special emphasis on atherogenesis.


Assuntos
Aterosclerose/tratamento farmacológico , Vildagliptina/uso terapêutico , Animais , Pressão Sanguínea , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Humanos , Inflamação/tratamento farmacológico , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico , Vildagliptina/farmacologia
2.
Chemosphere ; 246: 125661, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31891846

RESUMO

Neonicotinoids are increasingly being used for pest control, and their potential health risks are now receiving attention. In this study, the toxic effects of three neonicotinoids (dinotefuran, nitenpyram and acetamiprid) were evaluated in ICR mice. After 30 days of exposure to neonicotinoids (1/200 LD50), oxidative stress levels, biochemical parameters, free fatty acids contents, and 1H NMR-based hepatic metabolomics were tested. All treatment groups showed signs of amino acid metabolism disorders especially elevated branched chain amino acids and phenylalanine. Furthermore, animals exposed to neonicotinoids had elevated lipid levels, which induced oxidative stress. Overall, we found that oxidative stress is a common toxic effect of exposure to neonicotinoids. In addition, lipid accumulation induced by amino acid metabolism disorder may be the cause of oxidative stress. Our results further our understanding of the toxicological effects of neonicotinoids on mammals.


Assuntos
Inseticidas/toxicidade , Neonicotinoides/toxicidade , Estresse Oxidativo/fisiologia , Aminoácidos/metabolismo , Animais , Guanidinas , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Nitrocompostos , Testes de Toxicidade
3.
Continuum (Minneap Minn) ; 25(6): 1732-1766, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31794469

RESUMO

PURPOSE OF REVIEW: This article provides an overview of mitochondrial and metabolic biology, the genetic mechanisms causing mitochondrial diseases, the clinical features of mitochondrial diseases, lipid myopathies, and glycogen storage diseases, all with a focus on those syndromes and diseases associated with myopathy. Over the past decade, advances in genetic testing have revolutionized patient evaluation. The main goal of this review is to give the clinician the basic understanding to recognize patients at risk of these diseases using the standard history and physical examination. RECENT FINDINGS: Primary mitochondrial disease is the current designation for the illnesses resulting from genetic mutations in genes whose protein products are necessary for mitochondrial structure or function. In most circumstances, more than one organ system is involved in mitochondrial disease, and the value of the classic clinical features as originally described early in the history of mitochondrial diseases has reemerged as being important to identifying patients who may have a primary mitochondrial disease. The use of the genetic laboratory has become the most powerful tool for confirming a diagnosis, and nuances of using genetic results will be discussed in this article. Treatment for mitochondrial disease is symptomatic, with less emphasis on vitamin and supplement therapy than in the past. Clinical trials using pharmacologic agents are in progress, with the field attempting to define proper goals of treatment. Several standard accepted therapies exist for many of the metabolic myopathies. SUMMARY: Mitochondrial, lipid, and glycogen diseases are not uncommon causes of multisystem organ dysfunction, with the neurologic features, especially myopathy, occurring as a predominant feature. Early recognition requires basic knowledge of the varied clinical phenotypes before moving forward with a screening evaluation and possibly a genetic evaluation. Aside from a few specific diseases for which there are recommended interventions, treatment for the majority of these disorders remains symptomatic, with clinical trials currently in progress that will hopefully result in standard treatments.


Assuntos
Doença de Depósito de Glicogênio , Transtornos do Metabolismo dos Lipídeos , Doenças Mitocondriais , Doenças Musculares , Adolescente , Idoso , Feminino , Doença de Depósito de Glicogênio/diagnóstico , Doença de Depósito de Glicogênio/genética , Doença de Depósito de Glicogênio/fisiopatologia , Humanos , Transtornos do Metabolismo dos Lipídeos/diagnóstico , Transtornos do Metabolismo dos Lipídeos/genética , Transtornos do Metabolismo dos Lipídeos/fisiopatologia , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/genética , Doenças Mitocondriais/fisiopatologia , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Doenças Musculares/metabolismo , Doenças Musculares/fisiopatologia
4.
Gynecol Endocrinol ; 35(sup1): 41-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532320

RESUMO

Objective: To study clinical and laboratory parameters and morphological characteristics of the endometrium in women with impaired fat metabolism and failed IVF attempts. Materials and methods: Clinical examination, laboratory tests, morphological analysis, and immunohistochemistry of the endometrium were conducted in 76 patients with different BMI, followed up with infertility and failed IVF attempts. Patients were divided into four groups by body mass index (BMI): 1 group - 17 women with overweight, BMI = 25.0 - 29.9 kg/m2; 2 group - 15 women with class I obesity, BMI 30.0-34.9 kg/m2; 3 group - 14 women with class II obesity, BMI 35.0-39.9 kg/m2; and the control group of 30 women with normal weight, BMI 18.5-24.9 kg/m2. Results: Clinical and laboratory analysis revealed menstrual irregularities and hormonal imbalance such as hypoestrogenism. Immunohistochemistry of the endometrium found a significant decrease in the expression of ERα and PR receptors in the glands correlated to increasing BMI. Conclusion: Pregravid preparation of women with increased BMI and failed IVF attempts has to include life-style modification and weight reduction program to restore normal hormonal status and expression of estrogen and progesterone receptors, prevention of excessive proliferative processes in the endometrium, and improving endometrial receptivity.


Assuntos
Endométrio/patologia , Fertilização In Vitro , Infertilidade Feminina/patologia , Infertilidade Feminina/terapia , Transtornos do Metabolismo dos Lipídeos/patologia , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Endométrio/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/metabolismo , Estilo de Vida , Transtornos do Metabolismo dos Lipídeos/complicações , Transtornos do Metabolismo dos Lipídeos/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Sobrepeso/complicações , Sobrepeso/metabolismo , Sobrepeso/patologia , Receptores de Progesterona/metabolismo , Falha de Tratamento , Adulto Jovem
5.
Acta Biochim Biophys Sin (Shanghai) ; 51(9): 890-899, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31384916

RESUMO

Chlorpyrifos (CPF) is a widely used insecticide in pest control, and it can affect aquatic animals by contaminating the water. In this study, larval zebrafish were exposed to CPF at concentrations of 30, 100 and 300 µg/l for 7 days. In the CPF-treated group, lipid droplet accumulation was reduced in larval zebrafish. The levels of triglyceride (TG), total cholesterol (TC), and pyruvate were also decreased after CPF exposure. Cellular apoptosis were significantly increased in the heart tissue after CPF exposure compared with the control. Transcription changes in cardiovascular genes were also observed. Through transcriptome analysis, we found that the transcription of 465 genes changed significantly, with 398 upregulated and 67 downregulated in the CPF-treated group, indicating that CPF exposure altered the transcription of genes. Among these altered genes, a number of genes were closely related to the glucose and lipid metabolism pathways. Furthermore, we also confirmed that the transcription of genes related to fatty acid synthesis, TC synthesis, and lipogenesis were significantly decreased in larval zebrafish after exposure to CPF. These results indicated that CPF exposure induced lipid metabolism disorders associated with cardiovascular toxicity in larval zebrafish.


Assuntos
Clorpirifos/toxicidade , Inseticidas/toxicidade , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Peixe-Zebra , Animais , Modelos Animais de Doenças , Larva/efeitos dos fármacos , Larva/metabolismo , Transcriptoma , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
6.
Adv Exp Med Biol ; 1165: 195-232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399967

RESUMO

Finding new therapeutic targets of glomerulosclerosis treatment is an ongoing quest. Due to a living environment of various stresses and pathological stimuli, podocytes are prone to injuries; moreover, as a cell without proliferative potential, loss of podocytes is vital in the pathogenesis of glomerulosclerosis. Thus, sufficient understanding of factors and underlying mechanisms of podocyte injury facilitates the advancement of treating and prevention of glomerulosclerosis. The clinical symptom of podocyte injury is proteinuria, sometimes with loss of kidney functions progressing to glomerulosclerosis. Injury-induced changes in podocyte physiology and function are actually not a simple passive process, but a complex interaction of proteins that comprise the anatomical structure of podocytes at molecular levels. This chapter lists several aspects of podocyte injuries along with potential mechanisms, including glucose and lipid metabolism disorder, hypertension, RAS activation, micro-inflammation, immune disorder, and other factors. These aspects are not technically separated items, but intertwined with each other in the pathogenesis of podocyte injuries.


Assuntos
Glomerulosclerose Segmentar e Focal/fisiopatologia , Podócitos/citologia , Podócitos/patologia , Humanos , Hipertensão , Inflamação , Transtornos do Metabolismo dos Lipídeos , Proteinúria
7.
Adv Exp Med Biol ; 1165: 525-541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399983

RESUMO

Since the lipid nephrotoxicity hypothesis was proposed in 1982, increasing evidence has supported the hypothesis that lipid abnormalities contributed to the progression of glomerulosclerosis. In this chapter, we will discuss the general promises of the original hypothesis, focusing especially on the role of lipids and metabolic inflammation accompanying CKD in renal fibrosis and potential new strategies of prevention.


Assuntos
Nefropatias/fisiopatologia , Transtornos do Metabolismo dos Lipídeos/fisiopatologia , Progressão da Doença , Fibrose , Humanos , Inflamação , Lipídeos
8.
Medicina (Kaunas) ; 55(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412670

RESUMO

BACKGROUND AND OBJECTIVES: The Studies have suggested hypercholesterolemia is a risk factor for cerebrovascular disease. However, few of the studies with a small number of patients had tested the effect of hypercholesterolemia on the outcomes and complications among acute ischemic stroke (AIS) patients. We hypothesized that lipid disorders (LDs), though risk factors for AIS, were associated with better outcomes and fewer post-stroke complications. MATERIALS AND METHOD: We performed a retrospective analysis of the Nationwide Inpatient Sample (years 2003-2014) in adult hospitalizations for AIS to determine the outcomes and complications associated with LDs, using ICD-9-CM codes. In 2014, we also aimed to estimate adjusted odds of AIS in patients with LDs compared to patients without LDs. The multivariable survey logistic regression models, weighted to account for sampling strategy, were fitted to evaluate relationship of LDs with AIS among 2014 hospitalizations, and outcomes and complications amongst AIS patients from2003-2014. RESULTS AND CONCLUSIONS: In 2014, there were 28,212,820 (2.02% AIS and 5.50% LDs) hospitalizations. LDs patients had higher prevalence and odds of having AIS compared with non-LDs. Between 2003-2014, of the total 4,224,924 AIS hospitalizations, 451,645 (10.69%) had LDs. Patients with LDs had lower percentages and odds of mortality, risk of death, major/extreme disability, discharge to nursing facility, and complications including epilepsy, stroke-associated pneumonia, GI-bleeding and hemorrhagic-transformation compared to non-LDs. Although LDs are risk factors for AIS, concurrent LDs in AIS is not only associated with lower mortality and disability but also lower post-stroke complications and higher chance of discharge to home.


Assuntos
Isquemia Encefálica/complicações , Pacientes Internados/estatística & dados numéricos , Transtornos do Metabolismo dos Lipídeos/complicações , Alta do Paciente/estatística & dados numéricos , Acidente Vascular Cerebral/complicações , Idoso , Feminino , Mortalidade Hospitalar/tendências , Hospitalização , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Inquéritos e Questionários
9.
Biomed Environ Sci ; 32(6): 406-418, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262386

RESUMO

OBJECTIVE: Previous studies have indicated that the plasticizer di (2-ethylhexyl) phthalate (DEHP) affects lipid accumulation; however, its underlying mechanism remains unclear. We aim to clarify the effect of DEHP on lipid metabolism and the role of TYK2/STAT1 and autophagy. METHODS: In total, 160 Wistar rats were exposed to DEHP [0, 5, 50, 500 mg/(kg•d)] for 8 weeks. Lipid levels, as well as mRNA and protein levels of TYK2, STAT1, PPARγ, AOX, FAS, LPL, and LC3 were detected. RESULTS: The results indicate that DEHP exposure may lead to increased weight gain and altered serum lipids. We observed that DEHP exposure affected liver parenchyma and increased the volume or number of fat cells. In adipose tissue, decreased TYK2 and STAT1 promoted the expression of PPARγ and FAS. The mRNA and protein expression of LC3 in 50 and 500 mg/(kg•d) groups was increased significantly. In the liver, TYK2 and STAT1 increased compensatorily; however, the expression of FAS and AOX increased, while LPL expression decreased. Joint exposure to both a high-fat diet and DEHP led to complete disorder of lipid metabolism. CONCLUSION: It is suggested that DEHP induces lipid metabolism disorder by regulating TYK2/STAT1. Autophagy may play a potential role in this process as well. High-fat diet, in combination with DEHP exposure, may jointly have an effect on lipid metabolism disorder.


Assuntos
Autofagia/efeitos dos fármacos , Dietilexilftalato/toxicidade , Disruptores Endócrinos/toxicidade , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos Wistar , Fator de Transcrição STAT1/metabolismo , TYK2 Quinase/metabolismo
10.
Lipids Health Dis ; 18(1): 151, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286991

RESUMO

BACKGROUND: Free fatty acid (FFA) accumulation in proximal tubules plays a fundamental role in the progress of kidney disease. Here, we reported a rare case with undetectable serum FFAs and further evaluated the changes of serum FFAs in patients with chronic renal failure (CRF). METHODS: We analyzed the clinical data of a rare case and 574 CRF patients. The mRNA expression of lipoprotein lipase (LPL), hepatic lipase (HL) and fatty acid synthase (FASN) were determined in the rare case and 30 age-matched healthy males with qPCR. RESULTS: This rare case had serious proteinuria, hyperglycemia, lipid disorders and bilateral renal glomerular filtration dysfunction. Compared with healthy males, this case showed a 1.49-fold increase of LPL expression (P < 0.01), a 3.38-fold reduction of HL expression (P < 0.001), and no significant change of FASN expression (P > 0.05). In total, 21.6% of CRF patients showed abnormal FFAs. Biochemical parameters such as blood urea nitrogen (BUN) and creatinine (CREA) significantly differed among groups with low-, normal- or high-level-FFAs. Moreover, serum FFAs was found to be associated with BUN. FFAs decreased in the group with higher BUN (> 17.4 mmol/L) and in the group with lower estimated glomerular filtration rate (eGFR) (< 15 mL/min/1.73m2). CONCLUSIONS: The proteinuria, HL low expression and renal function failure may contribute to the FFA reduction, which might imply that the renal function is severely damaged.


Assuntos
Ácidos Graxos não Esterificados/sangue , Falência Renal Crônica/sangue , Adulto , Idoso , Análise Química do Sangue , Estudos de Casos e Controles , Ácido Graxo Sintase Tipo I/genética , Feminino , Expressão Gênica , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/fisiopatologia , Lipase/genética , Transtornos do Metabolismo dos Lipídeos/sangue , Transtornos do Metabolismo dos Lipídeos/etiologia , Lipase Lipoproteica/genética , Masculino , Pessoa de Meia-Idade , Proteinúria/sangue , Proteinúria/etiologia
11.
Rev Invest Clin ; 71(3): 157-167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184331

RESUMO

Obesity is associated with an increase of several metabolic disorders leading to the development of diseases such as type 2 diabetes and cardiovascular disease. This is due in part to the ectopic accumulation of triglycerides in organs that are non-adipose tissues, leading to lipotoxicity. Particularly, in the liver, the accumulation of lipids, mainly of triglycerides, leads to the formation of fatty liver. The accumulation of lipids in skeletal muscle and pancreas associates with insulin resistance and a decrease in insulin secretion, respectively. In addition, it has been suggested that dysbiosis of the gut microbiota can contribute to the process of lipid accumulation in non-adipose tissues, especially in the liver. The aim of the present review is to highlight the mechanisms associated with the development of lipotoxicity, and how with the advances in nutrigenomics, it is now possible to understand the molecular mechanisms by which some nutrients can attenuate the ectopic accumulation of triglycerides in non-adipose tissues. Particularly, we emphasize research conducted on the molecular mechanisms of action of soy protein and some of its isoflavones, and how these can reduce lipotoxicity by preventing the accumulation of lipids in the liver, skeletal muscle, and pancreas, as well as their role on the gut microbiota to attenuate the development of fatty liver. Thus, nutrigenomics is opening new dietary strategies based on several functional foods that can be used to ameliorate the pathologies associated with lipotoxicity.


Assuntos
Nutrigenômica , Obesidade/complicações , Proteínas de Soja/farmacologia , Animais , Humanos , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/prevenção & controle
12.
Hum Mol Genet ; 28(R1): R49-R54, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31227825

RESUMO

The prevalence of lipid disorders is alarmingly increasing in the Western world. They are the result of either primary causes, such as unhealthy lifestyle choices or inherited risk factors, or secondary causes like other diseases or medication. Atypical changes in the synthesis, processing and catabolism of lipoprotein particles may lead to severe hypercholesterolemia, hypertriglyceridemia or elevated Lp(a). Although cholesterol-lowering drugs are the most prescribed medications, not all patients achieve guideline recommended cholesterol levels with the current treatment options, emphasising the need for new therapies. Also, some lipid disorders do not have any treatment options but rely only on stringent dietary restriction. Patients with untreated lipid disorders carry a severe risk of cardiovascular disease, diabetes, non-alcoholic fatty liver disease and pancreatitis among others. To achieve better treatment outcome, novel selective gene expression and epigenetic targeting therapies are constantly being developed. Therapeutic innovations employing targeted RNA technology utilise small interfering RNAs, antisense oligonucleotides, long non-coding RNAs and microRNAs to regulate target protein production whereas viral gene therapy provides functional therapeutic genes and CRISPR/Cas technology relies on gene editing and transcriptional regulation. In this review, we will discuss the latest advances in clinical trials for novel lipid-lowering therapies and potential new targets in pre-clinical phase.


Assuntos
Transtornos do Metabolismo dos Lipídeos/terapia , Animais , Ensaios Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Suscetibilidade a Doenças , Avaliação Pré-Clínica de Medicamentos , Terapia Genética/métodos , Vetores Genéticos/genética , Humanos , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Transtornos do Metabolismo dos Lipídeos/etiologia , Transtornos do Metabolismo dos Lipídeos/metabolismo , Resultado do Tratamento
13.
Curr Opin Cardiol ; 34(4): 406-412, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31169601

RESUMO

PURPOSE OF REVIEW: Extensive work has gone into understanding the genetics of cardiovascular disease (CVD) and implicating genes involved in hyperlipidaemia. Translation into routine practise involves using genetic risk scores (GRS) to identify high-risk individuals in the general population. Some of these risk scores are beginning to disentangle the complex nature of CVD and inherited dyslipidaemias. RECENT FINDINGS: GRS of varying complexity have been used to identify high-risk groups of patients with polygenic CVD including some individuals with risk equivalent to monogenic disease. In phenotypic familial hypercholesterolaemia a six or 12 gene lipid GRS may identify polygenic cases that comprise up to 50% of cases. In high triglyceride syndromes including even cases of familial chylomicronaemia syndrome more than 80% of cases are polygenic and not even associated with rare variants. In both familial hypercholesterolaemia and familial chylomicronaemia syndrome individuals with polygenic disease have a lower risk than those with monogenic disease. SUMMARY: GRS show promise in identifying individuals with high risks of CVD. They have a close relationship with imaging markers. It is unclear whether GRS, imaging or both will be used to identify individuals at high risk of future events.


Assuntos
Transtornos do Metabolismo dos Lipídeos/genética , Predisposição Genética para Doença , Humanos , Fatores de Risco , Triglicerídeos
14.
Nutrients ; 11(5)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052523

RESUMO

Free sugars overconsumption is associated with an increased prevalence of risk factors for metabolic diseases such as the alteration of the blood lipid levels. Natural fruit juices have a free sugar composition quite similar to that of sugar-sweetened beverages. Thus, could fruit juice consumption lead to the same adverse effects on health as sweetened beverages? We attempted to answer this question by reviewing the available evidence on the health effects of both sugar-sweetened beverages and natural fruit juices. We determined that, despite the similarity of fruits juices to sugar-sweetened beverages in terms of free sugars content, it remains unclear whether they lead to the same metabolic consequences if consumed in equal dose. Important discrepancies between studies, such as type of fruit juice, dose, duration, study design, and measured outcomes, make it impossible to provide evidence-based public recommendations as to whether the consumption of fruit juices alters the blood lipid profile. More randomized controlled trials comparing the metabolic effects of fruit juice and sugar-sweetened beverage consumption are needed to shape accurate public health guidelines on the variety and quantity of free sugars in our diet that would help to prevent the development of obesity and related health problems.


Assuntos
Bebidas/análise , Sucos de Frutas e Vegetais/análise , Edulcorantes/análise , Adolescente , Adulto , Idoso , Sacarose na Dieta/efeitos adversos , Feminino , Frutose/metabolismo , Glucose/metabolismo , Transtornos do Metabolismo de Glucose/etiologia , Xarope de Milho Rico em Frutose/efeitos adversos , Humanos , Transtornos do Metabolismo dos Lipídeos/etiologia , Masculino , Pessoa de Meia-Idade , Nutrientes , Fatores de Risco , Adulto Jovem
15.
Food Funct ; 10(5): 2560-2572, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-30994668

RESUMO

The purpose of this study was to assess the potential effects of polysaccharides from edible mushroom Grifola frondosa (GFP) on lipid metabolic disorders and gut microbiota dysbiosis, and elucidate their possible regulatory mechanisms on lipid and cholesterol metabolism in high-fat diet (HFD)-exacerbated hyperlipidemic and hypercholesterolemic rats. Results showed that oral administration of GFP markedly alleviated dyslipidaemia through decreasing the serum levels of total triglycerides, total cholesterol, and free fatty acids, and significantly suppressing hepatic lipid accumulation and steatosis. Besides, the excretion of fecal bile acids was also promoted by oral administration of GFP. Metagenomic analysis revealed that GFP supplementation (400 mg kg-1 day-1) resulted in significant structure changes on gut microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. Key microbial phylotypes responding to GFP intervention were identified to strongly correlate with the lipid metabolism disorder associated parameters using the correlation network based on Spearman's correlation coefficient. Serum and hepatic lipid profiles were found positively correlated with Clostridium-XVIII, Butyricicoccus and Turicibacter, but negatively correlated with Helicobater, Intestinimonas, Barnesiella, Parasutterella, Ruminococcus and Flavonifracter. Moreover, GFP treatment (400 mg kg-1 day-1) regulated the mRNA expression levels of the genes responsible for hepatic lipid and cholesterol metabolism. Oral supplementation of GFP markedly increased the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acid (BA) synthesis and excretion from the liver. These findings illustrated that GFP could ameliorate lipid metabolic disorders through modulating specific gut microbial phylotypes and regulating hepatic lipid and cholesterol metabolism related genes, and therefore could be used as a potential functional food ingredient for the prevention or treatment of hyperlipidemia.


Assuntos
Disbiose/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Grifola/química , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Colesterol/sangue , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Disbiose/metabolismo , Disbiose/microbiologia , Ácidos Graxos não Esterificados/sangue , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Transtornos do Metabolismo dos Lipídeos/genética , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/microbiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Triglicerídeos/sangue
16.
Metabolism ; 95: 8-20, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30878493

RESUMO

BACKGROUND: The peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response and development. Numerous studies relying on tissue-specific invalidation of the Pparg gene have shown distinct facets of its activity, whereas the effects of its systemic inactivation remain unexplored due to embryonic lethality. By maintaining PPARγ expression in the placenta, we recently generated a mouse model carrying Pparg full body deletion (PpargΔ/Δ), which in contrast to a previously published model is totally deprived of any form of adipose tissue. Herein, we propose an in-depth study of the metabolic alterations observed in this new model. METHODS: Young adult mice, both males and females analyzed separately, were first phenotyped for their gross anatomical alterations. Systemic metabolic parameters were analyzed in the blood, in static and in dynamic conditions. A full exploration of energy metabolism was performed in calorimetric cages as well as in metabolic cages. Our study was completed by expression analyses of a set of specific genes. MAIN FINDINGS: PpargΔ/Δ mice show a striking complete absence of any form of adipose tissue, which triggers a complex metabolic phenotype including increased lean mass with organomegaly, hypermetabolism, urinary energy loss, hyperphagia, and increased amino acid metabolism. PpargΔ/Δ mice develop severe type 2 diabetes, characterized by hyperglycemia, hyperinsulinemia, polyuria and polydispsia. They show a remarkable metabolic inflexibility, as indicated by the inability to shift substrate oxidation between glucose and lipids, in both ad libitum fed state and fed/fasted/refed transitions. Moreover, upon fasting PpargΔ/Δ mice enter a severe hypometabolic state. CONCLUSIONS: Our data comprehensively describe the impact of lipoatrophy on metabolic homeostasis. As such, the presented data on PpargΔ/Δ mice gives new clues on what and how to explore severe lipodystrophy and its subsequent metabolic complications in human.


Assuntos
Diabetes Mellitus Tipo 2/genética , Transtornos do Metabolismo dos Lipídeos/genética , Tamanho do Órgão/genética , PPAR gama/genética , Tecido Adiposo/anatomia & histologia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/genética , Feminino , Deleção de Genes , Glucose/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Lipodistrofia/genética , Lipodistrofia/metabolismo , Camundongos , Gravidez
17.
Diabetes Metab Res Rev ; 35(5): e3142, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30767421

RESUMO

OBJECTIVES: Pancreas steatosis is the description of fat accumulation in the pancreatic gland. The prevalence and development mechanisms of pancreatic steatosis in patients with metabolic disorders still remain unclear. The aim of this study is to systematically review the association between pancreatic steatosis and metabolic co-morbidities. METHODS: We performed a systematic search strategy using three electronic databases (MEDLINE, Scopus, and Embase) for relevant studies concerning the associations of pancreatic steatosis with metabolic syndrome (MetS) and its clinical relevance from inception until 30 September 2018. RESULTS: One thousand three hundred fifty one references were identified in the initial search, and a total of 13 studies involving 49 329 subjects were included. This analyses elucidated the presence of non-alcoholic fatty pancreas disease (NAFPD) and was associated with a significant increased risk of metabolic syndrome (RR = 2.25; 95% CI, 2.00-2.53; P < 0.0001; I2  = 42.8%; eight studies included), hypertension (RR = 1.43; 95% CI, 1.08-1.90; P = 0.013; I2  = 94.7%; nine studies included), non-alcoholic fatty liver disease (NAFLD) (RR = 2.49; 95% CI, 2.06-3.02; P < 0.0001; I2  = 96.9%; nine studies included), diabetes mellitus (RR = 1.99; 95% CI, 1.18-3.35; P = 0.01; I2  = 97.6%; 10 studies included), and central obesity (RR = 1.91; 95% CI, 1.67-2.19; P < 0.0001; I2  = 95.9%; six studies included). The association between NAFPD and hyperlipidaemia was not statistically significant (RR = 1.33; 95% CI, 0.82-2.17; P = 0.249; I2  = 97%; five studies included). CONCLUSIONS: The existing evidence indicates that NAFPD is significantly associated with an increased risk of metabolic syndrome and its components. Well-designed prospective cohort studies between pancreatic steatosis and MetS are needed to elaborate the causality in the future.


Assuntos
Transtornos do Metabolismo dos Lipídeos/epidemiologia , Síndrome Metabólica/epidemiologia , Pancreatopatias/epidemiologia , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/metabolismo , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/epidemiologia , Transtornos do Metabolismo dos Lipídeos/complicações , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Pancreatopatias/complicações , Prevalência , Fatores de Risco
18.
Lung Cancer ; 127: 122-129, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30642540

RESUMO

OBJECTIVES: In presence of lung cancer, the additional impact of comorbidity on survival is often neglected, although comorbidities are likely to be prevalent. Our study examines the comorbidity profile and the impact of distinct conditions on survival in German lung cancer patients. MATERIAL AND METHODS: We investigated claims data from a large nationwide statutory health insurance fund of 16,202 patients initially diagnosed with lung cancer in 2009. We calculated the prevalence of comorbidities grouped according to an extension of the Elixhauser Comorbidity Index (EI). Effects of distinct comorbidities on 5-year survival were examined using multivariate Cox proportional hazards models, adjusted for sex, age and metastases at baseline. All analyses were stratified by initial lung cancer-related treatment regimen (Surgery, Chemotherapy/Radiotherapy, No treatment). Findings were visualized in the form of a comorbidome. RESULTS: Our study population was predominantly male (70.6%) with a mean age of 68.6 years, and a mean EI score of 3.94. Patients without treatment were older (74.4 years), and their comorbidity burden was higher (mean EI = 4.59). Median survival varied by subgroup (Surgery: 24.4 months, Chemotherapy/Radiotherapy: 8.8 months, No treatment: 2.0 months), and so did the comorbidity profile and the impact of distinct conditions on survival. Generally, the effect of comorbidities on survival was detrimental and the negative association was most pronounced for 'Weight Loss' and' Paralysis'. In contrast, 'Lipid Metabolism Disorders' and 'Obesity' were positively associated with survival. Noteworthily, highly prevalent conditions tended not to show any significant association. CONCLUSION: We found specific comorbidity profiles within the distinct treatment regimens. Moreover, there were negative but also some positive associations with survival, and the strength of these effects varied by stratum. Particularly the positive effects of 'Obesity" and 'Lipid Metabolism Disorders' which were robust across strata need to be further investigated to elucidate potential biomedical explanations.


Assuntos
Transtornos do Metabolismo dos Lipídeos/epidemiologia , Neoplasias Pulmonares/epidemiologia , Obesidade/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sobrevida
19.
Pathology ; 51(2): 193-201, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30598327

RESUMO

Rare genetic lipid disorders affect the levels of cholesterol and/or triglyceride in the circulation and, if untreated, can often lead to severe multisystem complications. The field of rare lipid disorders is evolving and increasing awareness of these conditions, along with the systematic integration of recent advances or knowledge into clinical practice, is crucial to improve patient outcomes. The aim of this review is to provide an overview of selected rare genetic lipid disorders, focusing on the recommended diagnostic strategies and contemporary treatment and management options.


Assuntos
Transtornos do Metabolismo dos Lipídeos/diagnóstico , Metabolismo dos Lipídeos , Doenças Raras/diagnóstico , Colesterol/metabolismo , Humanos , Transtornos do Metabolismo dos Lipídeos/genética , Transtornos do Metabolismo dos Lipídeos/terapia , Doenças Raras/genética , Doenças Raras/terapia , Triglicerídeos/metabolismo
20.
Vet Pathol ; 56(2): 282-288, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30244665

RESUMO

The Quaker parrot has been used as a psittacine model to study clinical lipidology and lipid-related disorders. However, while Quaker parrots appear to be anecdotally susceptible to a variety of spontaneous dyslipidemic disorders and lesions caused by excess lipid accumulation, epidemiologic data are lacking. A multicenter retrospective study on 652 pathology submissions (411 necropsies and 243 biopsies) from Quaker parrots was performed by recording the final pathological diagnoses, age, and sex for each bird. The prevalence of lesions associated with lipid metabolism, such as hepatic lipidosis, atherosclerosis, xanthomas, adipose tumors, coelomic steatitis/steatonecrosis, endogenous lipid pneumonia, and acute pancreatic necrosis/pancreatitis, was reported. Multiple logistic regression models were used to characterize the effects of sex and age on these lesions, and the prevalence of hepatic lipidosis and atherosclerosis was compared to those in a random sample of control psittacine birds. The raw prevalence of atherosclerosis and hepatic lipidosis was 5.6% (95% confidence interval [CI], 3.4%-7.8%) and 21.2% (95% CI, 17.2%-25.1%), respectively. While the prevalence of atherosclerosis was similar to other psittacine species, hepatic lipidosis was more common in Quaker parrots. Quaker parrots also showed a unique susceptibility to acute pancreatic necrosis with a prevalence of 12.9% (95% CI, 9.7%-16.1%). Male parrots were found to be more susceptible than females to lipid accumulation lesions ( P = .0024), including atherosclerosis ( P = .018) and hepatic lipidosis ( P < .001). This retrospective study confirms the high susceptibility of Quaker parrots to lipid-related disorders and presents epidemiological data that may be useful to avian clinicians, pathologists, and researchers using Quaker parrots.


Assuntos
Doenças das Aves/patologia , Transtornos do Metabolismo dos Lipídeos/veterinária , Papagaios , Animais , Aterosclerose/diagnóstico , Aterosclerose/patologia , Aterosclerose/veterinária , Doenças das Aves/diagnóstico , Feminino , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/diagnóstico , Transtornos do Metabolismo dos Lipídeos/patologia , Lipidoses/diagnóstico , Lipidoses/patologia , Lipidoses/veterinária , Hepatopatias/diagnóstico , Hepatopatias/patologia , Hepatopatias/veterinária , Masculino , Pneumonia Lipoide/diagnóstico , Pneumonia Lipoide/patologia , Pneumonia Lipoide/veterinária , Estudos Retrospectivos , Fatores Sexuais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA