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1.
Nursing ; 50(3): 32-39, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32068703

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is defined as storage of excess fat in the liver not caused by heavy alcohol consumption. Nonalcoholic steatohepatitis is the severe form of NAFLD. This article discusses causes, diagnosis, and nursing interventions for patients with either disorder.


Assuntos
Hepatopatia Gordurosa não Alcoólica/enfermagem , Humanos , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica/etiologia , Avaliação em Enfermagem , Diagnóstico de Enfermagem , Educação de Pacientes como Assunto , Fatores de Risco , Índice de Gravidade de Doença
2.
Life Sci ; 241: 117086, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31756344

RESUMO

BACKGROUND/AIMS: Recent studies have found vitamin D deficiency promotes fat deposition into the hepatocytes, thus contributing to the development of nonalcoholic fatty liver disease (NAFLD), which is a hepatic manifestation of metabolic syndrome. This study aimed to investigate the potential effects of vitamin D on NAFLD with the involvement of the p53 pathway. METHODS: Initially, an in vivo high-fat diet (HFD)-induced NAFLD mouse model was established. Then the HFD-induced NAFLD mice were treated with vitamin D. Next, the serum levels of TNF-α, GSH-px and malondialdehyde (MDA) were assessed using ELISA and ROS content was evaluated by flow cytometry, followed by the measurement of expression of Duox1, Duox2, SOD1, SOD2, PRDX1 I, ACC, SREBP1c, MTTP, PPARα, p53, p21 and p16 using RT-qPCR and Western blot analysis. Positive expression of FAS and FASL proteins was measured using immunohistochemistry. TUNEL and Senescence-associated ß-galactosidase (SA-ß-Gal) staining were subsequently conducted to assess the senescence and apoptosis of hepatocytes. RESULTS: HFD-induced mice treated with vitamin D presented with significantly increased GSH-px levels, as well as protein expression of SOD1, SOD2, PRDX1, MTTP and PPARα, but decreased MDA and ROS levels, expression of Duox1, Duox2, ACC, SREBP1c, p53, p21 and p16, positive expression of FAS and FASL proteins as well as impaired senescence and apoptosis of hepatocytes. CONCLUSION: Active vitamin D supplementation could potentially impede hepatocyte senescence and apoptosis via suppression of the p53 pathway, thus preventing the progression of NAFLD. Our study provides available evidence on the potential clinical utility of vitamin D supplementation in NAFLD.


Assuntos
Hepatócitos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Proteína Supressora de Tumor p53/metabolismo , Vitamina D/farmacologia , Animais , Apoptose/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Proteína Ligante Fas/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Redes e Vias Metabólicas/efeitos dos fármacos , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas/metabolismo , Esteroide Hidroxilases/genética , Proteína Supressora de Tumor p53/genética , Receptor fas/metabolismo
3.
Life Sci ; 241: 117163, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837337

RESUMO

AIMS: The high sugar and lipid content of the Western diet (WD) is associated with metabolic dysfunction, non-alcoholic steatohepatitis, and it is an established risk factor for neuropsychiatric disorders. Our previous studies reported negative effects of the WD on rodent emotionality, impulsivity, and sociability in adulthood. Here, we investigated the effect of the WD on motor coordination, novelty recognition, and affective behavior in mice as well as molecular and cellular endpoints in brain and peripheral tissues. MAIN METHODS: Female C57BL/6 J mice were fed the WD for three weeks and were investigated for glucose tolerance, insulin resistance, liver steatosis, and changes in motor coordination, object recognition, and despair behavior in the swim test. Lipids and liver injury markers, including aspartate-transaminase, alanine-transaminase and urea were measured in blood. Serotonin transporter (SERT) expression, the density of Iba1-positive cells and concentration of malondialdehyde were measured in brain. KEY FINDINGS: WD-fed mice exhibited impaired glucose tolerance and insulin resistance, a loss of motor coordination, deficits in novel object exploration and recognition, increased helplessness, dyslipidemia, as well as signs of a non-alcoholic steatohepatitis (NASH)-like syndrome: liver steatosis and increased liver injury markers. Importantly, these changes were accompanied by decreased SERT expression, elevated numbers of microglia cells and malondialdehyde levels in, and restricted to, the prefrontal cortex. SIGNIFICANCE: The WD induces a spectrum of behaviors that are more reminiscent of ADHD and ASD than previously recognized and suggests that, in addition to the impairment of impulsivity and sociability, the consumption of a WD might be expected to exacerbate motor dysfunction that is also known to be associated with adult ADHD and ASD.


Assuntos
Transtornos Cognitivos/etiologia , Dieta Ocidental/efeitos adversos , Inflamação/etiologia , Transtornos Motores/etiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Córtex Pré-Frontal/patologia , Animais , Comportamento Animal , Transtornos Cognitivos/patologia , Feminino , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transtornos Motores/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Córtex Pré-Frontal/imunologia
4.
J Sci Food Agric ; 100(4): 1787-1796, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31849065

RESUMO

BACKGROUND: This study evaluated the effects of hydroalcoholic extract of spinach (HES) on nonalcoholic fatty liver disease (NAFLD). In the prevention phase, 18 Sprague-Dawley rats were fed a high-fat diet, a high-fat diet plus 400 mg kg-1 HES, or a chow diet for 7 weeks. For the treatment phase, after the induction of NAFLD, they were fed a high-fat diet, a high-fat diet plus 400 mg kg-1 HES, a chow diet, or chow diet plus 400 mg kg-1 HES for 4 weeks (n = 6). RESULTS: Weight gain (P = 0.01), food intake (P < 0.01), serum glucose (P = 0.01), triglyceride (TG) (P = 0.02), low-density lipoprotein cholesterol (LDL-c) (P = 0.01), aspartate aminotransferase (AST) (P = 0.02), liver steatosis, and the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) (P < 0.01) in the high-fat group were statistically higher than in the other groups at the end of the prevention phase. Feeding spinach extract to rats on a high-fat diet decreased serum glucose (P = 0.01), total cholesterol (TCh) (P < 0.01), AST (P = 0.01), alkaline phosphatase (ALP) (P < 0.01), and liver steatosis (P < 0.01) in the treatment phase. CONCLUSION: Overall, spinach extract showed beneficial effects in the prevention and treatment of NAFLD. © 2019 Society of Chemical Industry.


Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Spinacia oleracea/química , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
5.
Nat Med ; 25(12): 1822-1832, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31806905

RESUMO

Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.


Assuntos
Doença Crônica/epidemiologia , Inflamação/fisiopatologia , Longevidade/genética , Doenças Autoimunes/etiologia , Doenças Autoimunes/fisiopatologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/fisiopatologia , Humanos , Inflamação/complicações , Inflamação/epidemiologia , Estilo de Vida , Longevidade/fisiologia , Neoplasias/etiologia , Neoplasias/fisiopatologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
8.
BMC Complement Altern Med ; 19(1): 294, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684925

RESUMO

BACKGOUND: Obesity and dyslipidemia are major risk factors associated with non-alcoholic fatty liver disease (NAFLD). NAFLD refers to the accumulation of fat in more than 5% of the liver without alcohol consumption. NAFLD is the most common liver disease and is rapidly becoming a global public health problem. Maoberry (Antidesma bunius) is a fruit rich in antioxidants, especially phenolic compounds, which are reported to have benefits for patients with NAFLD. METHODS: We evaluated the effect of Maoberry extract on fat metabolism in liver tissues of high fat diet-induced rats. Five (5) groups (n = 12) of male Sprague-Dawley (SD) rats were divided into those given a high fat diet with no treatment (HF), different dosages of Maoberry extracts (0.38 [ML], 0.76 [MM) and 1.52 [MH] g/kg body weight) and 10 mg/kg statin (STAT). The rats were fed a high fat diet for 4 weeks to induce obesity and subsequently continued more for 12 weeks with treatments of Maoberry extracts or STAT. The levels of triglyceride, liver enzymes, oxidative stress and inflammation markers, triglyceride synthesis regulators, and pathology of the liver in high fat diet-induced rats were investigated. RESULTS: Feeding Maoberry extract in MH groups resulted in decreasing levels of serum alanine aminotransferase (ALT), liver triglyceride, liver thiobarbituric acid reactive substances (TBARS) and mRNA expression of tumour necrosis factor (TNF)-α, interleukin (IL)-6, glycerol-3-phosphate acyltransferase (GPAT)-1 and acetyl-coenzyme A carboxylase (ACC) compared with the HF group (P < 0.05). Moreover, histopathological study of the liver showed reduced fat droplets in the Maoberry extract treatment groups, especially in MH groups and STAT treatment groups. CONCLUSIONS: The improvements of fat metabolism in liver tissues of rats fed a high-fat diet were observed in Maoberry extracts treatment groups. The underline mechanism that link to fat metabolism might be through the process accompanied with down-regulated the gene expression of key enzymes of lipid production, antioxidant activity, and anti-inflammation properties of Maoberry extracts which contains high levels of phenolic and flavonoid compounds.


Assuntos
Antioxidantes/administração & dosagem , Gorduras/metabolismo , Fígado/efeitos dos fármacos , Malpighiales/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Acetil-CoA C-Acetiltransferase/genética , Acetil-CoA C-Acetiltransferase/metabolismo , Animais , Antioxidantes/química , Dieta Hiperlipídica/efeitos adversos , Frutas/química , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
9.
Arq Gastroenterol ; 56(4): 431-439, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721969

RESUMO

The nonalcoholic fatty liver disease (NAFLD) affects approximately 20%-30% of general population and is even more prevalent among obese individuals. The risk factors mainly associated with NAFLD are diseases related to the metabolic syndrome, genetics and environment. In this review, we provide a literature compilation evaluating the evidence behind dietary components, including calories intake, fat, protein, fibers and carbohydrate, especially fructose which could be a trigger to development and progression of the NAFLD. In fact, it has been demonstrated that diet is an important factor for the development of NAFLD and its association is complex and extends beyond total energy intake.


Assuntos
Dieta/efeitos adversos , Ingestão de Energia , Hepatopatia Gordurosa não Alcoólica/etiologia , Progressão da Doença , Humanos , Fatores de Risco
10.
Presse Med ; 48(12): 1468-1483, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31767252

RESUMO

Non-Alcoholic Fatty Liver Disease (NAFLD) is a complex chronic disease resulting from an interaction between genetic and environmental factors. The phenotype and pathophysiology of NAFLD is heterogeneous. NAFLD is a continuum of histological lesions of the liver from steatosis, Non-Alcoholic SteatoHepatitis (NASH), NASH with fibrosis, cirrhosis to hepatocellular carcinoma. The pathophysiology encompasses a dysfunction in fatty tissue (sub-cutaneous and visceral) associated with insulin-resistance and metabolic inflammation. NAFLD is a "multi-systemic" disease. Reciprocal and aggravating interactions exist between NAFLD, cardiovascular anomalies and diabetes. The understanding of the mechanisms responsible for NAFLD allows the identification of potential novel therapeutic targets.


Assuntos
Hepatopatia Gordurosa não Alcoólica/etiologia , Tecido Adiposo/patologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Epigênese Genética/fisiologia , Predisposição Genética para Doença , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Inflamação/epidemiologia , Fígado/patologia , Microbiota/fisiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia
11.
Presse Med ; 48(12): 1502-1506, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31757736

RESUMO

Bariatric surgery is indicated for patients with BMI≥35kg/m2 and associated steatohepatitis. Bariatric surgery induces NASH disappearance for nearly 80% of patients after 1 year of follow up. Bariatric surgery is associated with low morbidity and mortality if patients are well selected. Bariatric surgery is contraindicated in patients with cirrhosis. Long-term data are needed to determine the risk of recurrence of NASH. The extension of indications for bariatric surgery to patients with BMI less than 35kg/m2 will depend on the results of randomized trials.


Assuntos
Cirurgia Bariátrica , Hepatopatia Gordurosa não Alcoólica/cirurgia , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/classificação , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/tendências , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Cuidados Pós-Operatórios/métodos
12.
Arq Gastroenterol ; 56(3): 270-275, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633724

RESUMO

BACKGROUND: Metabolic risk factors of non alcoholic fatty liver disease (NAFLD) in non diabetic teetotallers who constitute a definite group are not well defined. OBJECTIVE: To identify the metabolic risk factors of NAFLD if any in non diabetic subjects who do not consume alcohol. METHODS: In a cross sectional study the effect of metabolic parameters (BMI, individual lipid levels, hemoglobinA1c (HbA1c), HOMA IR and the metabolic syndrome components) of 150 consecutive non diabetic teetotallers (90 with normal glucose tolerance and 60 prediabetics) on their NFS (quantifiable severity parameter of NAFLD) was studied by linear regression analysis. Similar study was done in the normal glucose tolerance and prediabetes groups separately. These parameters were then compared with those of 75 matched diabetic teetotallers with NAFLD. To analyse further the difference between normal glucose tolerance, prediabetic and overt diabetic groups, binary logistic regression of the factors was carried out taking prediabetes and diabetes as outcome variable. RESULTS: All the metabolic parameters were significantly higher in diabetics compared to non diabetics and in prediabetics compared to those with normal glucose tolerance except high-density lipoprotein cholesterol. Triglyceride, high-density lipoprotein cholesterol and BMI significantly predicted NFS in the overall (adjusted R2 68.7%, P=0.000) and normal glucose tolerance groups (adjusted R2 73.2%, P=0.000) whereas BMI, triglyceride, low-density lipoprotein cholesterol and HbA1c did in prediabetics (adjusted R2 89%, P=0.000). The metabolic syndrome was significantly associated with NFS in the overall and prediabetic groups. High triglyceride (odds ratio1.08), low-density lipoprotein cholesterol (odds ratio1.03) and HbA1c (odds ratio 11.54) were positively associated with prediabetes compared to normal glucose tolerance group. CONCLUSION: In nondiabetic teetotallers dyslipidemias are the prime contributors to the development of NAFLD.


Assuntos
Dislipidemias/metabolismo , Resistência à Insulina/fisiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Dislipidemias/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/metabolismo , Fatores de Risco , Triglicerídeos/sangue
13.
Vnitr Lek ; 65(9): 577-582, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31635469

RESUMO

Along with the increasing incidence and prevalence of obesity and the metabolic syndrome, the number of patients with its hepatic manifestation - NAFL, characterized by triglyceride storage in liver, is rising. NAFL (non-alcoholic fatty liver) is now, with the prevalence of 40 %, the most common liver disease in Western countries. Despite that NAFL has usually no symptoms and in most patients, it is diagnosed as an incidental finding by abdominal ultra-sound, every third of these patients develops NASH (non-alcoholic steatohepatitis), resulting in an individual progression of the sequence of fibrosis - cirrhosis - hepatocellular carcinoma. Due to the fact, that NASH is, along with the cardiovascular causes, involved in liver-related mortality of patients with the metabolic syndrome, from clinical view, it is fundamental to distinguish between benign NAFL and potentially progressive NASH. This appears even more serious realizing that patients with NASH are being often underdiagnosed because of limited indications of liver biopsy, a common diagnostically gold standard. This work emphasizes the relationship between metabolic syndrome and liver disease and presents the main diagnostic possibilities of NAFL/NASH, the most dealing with serum markers. It is based on a research, using the PubMed database and putting the key words as search terms. Considering the huge number of patients diagnosed with fatty liver, a non-invasive, widely approachable method should be established, to make the diagnostic and staging of progression of NASH broadly possible. A new method using LCMS (Liquid Chromatography-Mass Spectrometry) analysis of serum lipids now fulfils these criteria, having high enough specificity and sensitivity, and have also been validated by comparing with a large cohort of patients diagnosed with liver biopsy.


Assuntos
Fígado Gorduroso , Cirrose Hepática , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico , Humanos , Cirrose Hepática/etiologia , Hepatopatia Gordurosa não Alcoólica/etiologia
14.
World J Gastroenterol ; 25(36): 5451-5468, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576092

RESUMO

BACKGROUND: Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD). AIM: To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro. METHODS: The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells. RESULTS: AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation; enhance steatogenesis, including promoting lipogenesis [sterol regulatory element-binding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid ß-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α]; accelerate proliferation; and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid dramatically improved liver injury and eliminated liver fat in NAFLD mice. CONCLUSION: AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.


Assuntos
Proteínas de Transporte/metabolismo , Glicoproteínas/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Tetracloreto de Carbono/toxicidade , Proteínas de Transporte/genética , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Regulação para Baixo , Técnicas de Silenciamento de Genes , Glicoproteínas/genética , Humanos , Lipogênese , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Oxirredução , Transdução de Sinais
15.
Int J Mol Sci ; 20(20)2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31618976

RESUMO

Non-alcoholic fatty liver disease (NAFLD) can progress from steatosis to non-alcoholic steatohepatitis (NASH) characterized by liver inflammation, possibly leading to cirrhosis and hepatocellular carcinoma (HCC). Mice with impaired macrophage activation, when fed a high-fat diet, develop severe NASH. Evidence is mounting that Kupffer cells are implicated. However, it is unknown whether the resident CD68+ or bone marrow-derived CD11b+ Kupffer cells are involved. Characterization of the FSP1cre-Pparb/d-/- mouse liver revealed that FSP1 is expressed in CD11b+ Kupffer cells. Although these cells only constitute a minute fraction of the liver cell population, Pparb/d deletion in these cells led to remarkable hepatic phenotypic changes. We report that a higher lipid content was present in postnatal day 2 (P2) FSP1cre-Pparb/d-/- livers, which diminished after weaning. Quantification of total lipids and triglycerides revealed that P2 and week 4 of age FSP1cre-Pparb/d-/- livers have higher levels of both. qPCR analysis also showed upregulation of genes involved in fatty acid ß-oxidation, and fatty acid and triglyceride synthesis pathways. This result is further supported by western blot analysis of proteins in these pathways. Hence, we propose that FSP1cre-Pparb/d-/- mice, which accumulate lipids in their liver in early life, may represent a useful animal model to study juvenile NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , PPAR beta/genética , Proteína A4 de Ligação a Cálcio da Família S100/genética , Animais , Biomarcadores , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Hepatócitos/metabolismo , Espaço Intracelular/metabolismo , Macrófagos do Fígado/metabolismo , Metabolismo dos Lipídeos , Camundongos , Camundongos Transgênicos , Modelos Biológicos , Oxirredução , PPAR beta/metabolismo , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo
16.
World J Gastroenterol ; 25(37): 5676-5686, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31602167

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a frequently reported condition in patients with inflammatory bowel disease (IBD). Both intestinal inflammation and metabolic factors are believed to contribute to the pathogenesis of IBD-associated NAFLD. AIM: To evaluate the prevalence of steatosis and liver fibrosis (LF) in a cohort of IBD patients and the identification of metabolic- and IBD-related risk factors for NAFLD and LF. METHODS: IBD patients were consecutively enrolled from December 2016 to January 2018. Demographic, anthropometric and biochemical data were collected so as eating habits. Abdominal ultrasound and transient elastography were performed to evaluate the presence of NAFLD and LF respectively. RESULTS: A total of 178 consecutive patients were enrolled and included in the analysis (95 Ulcerative colitis, 83 Crohn's disease). NAFLD was detected by imaging in 72 (40.4%) patients. Comparison between patients with and without NAFLD showed no significant differences in terms of IBD severity, disease duration, location/extension, use of IBD-related medications (i.e., steroids, anti-TNFs, and immunomodulators) and surgery. NAFLD was significantly associated with the presence of metabolic syndrome [MetS; odds ratio (OR): 4.13, P = 0.001] and obesity defined by body mass index (OR: 9.21, P = 0.0002). IBD patients with NAFLD showed higher caloric intake and lipid consumption than those without NAFLD, regardless disease activity. At the multivariate analysis, male sex, advanced age and high lipid consumption were independent risk factors for the development of NAFLD. An increased liver stiffness was detected in 21 patients (16%) and the presence of MetS was the only relevant factor associated to LF (OR: 3.40, P = 0.01). CONCLUSION: In this study, we demonstrate that risk factors for NAFLD and LF in the IBD population do not differ from those in the general population.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Cirrose Hepática/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Fatores Etários , Idoso , Gorduras na Dieta/efeitos adversos , Progressão da Doença , Feminino , Seguimentos , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Prevalência , Fatores de Risco , Fatores Sexuais
17.
Food Funct ; 10(9): 6170-6183, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31501836

RESUMO

High-fat-diet (HFD) feeding is associated with liver oxidative stress (OS), n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) depletion, hepatic steatosis and mitochondrial dysfunction. Our hypothesis is that the HFD-induced liver injury can be attenuated by the combined supplementation of n-3 LCPUFA eicosapentaenoic acid (EPA) and the antioxidant hydroxytyrosol (HT). The C57BL/6J mice were administered an HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg kg-1 day-1), HT (5 mg kg-1 day-1), or EPA + HT (50 and 5 mg kg-1 day-1, respectively) for 12 weeks. We measured the body and liver weights and dietary and energy intakes along with liver histology, FA composition, steatosis score and associated transcription factors, mitochondrial functions and metabolic factors related to energy sensing through the AMP-activated protein kinase (AMPK) and PPAR-γ coactivator-1α (PGC-1α) cascade. It was found that the HFD significantly induced liver steatosis, with a 66% depletion of n-3 LCPUFAs and a 100% increase in n-6/n-3 LCPUFA ratio as compared to the case of CD (p < 0.05). These changes were concomitant with (i) a 95% higher lipogenic and 70% lower FA oxidation signaling, (ii) a 40% diminution in mitochondrial respiratory capacity and (iii) a 56% lower ATP content. HFD-induced liver steatosis was also associated with (iv) a depressed mRNA expression of AMPK-PGC-1α signaling components, nuclear respiratory factor-2 (NRF-2) and ß-ATP synthase. These HFD effects were significantly attenuated by the combined EPA + HT supplementation in an additive manner. These results suggested that EPA and HT co-administration partly prevented HFD-induced liver steatosis, thus strengthening the importance of combined interventions in hepatoprotection in non-alcoholic fatty liver disease.


Assuntos
Ácido Eicosapentaenoico/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Álcool Feniletílico/análogos & derivados , Trifosfato de Adenosina/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Sinergismo Farmacológico , Ácidos Graxos Ômega-3/metabolismo , Fator de Transcrição de Proteínas de Ligação GA/genética , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Humanos , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Álcool Feniletílico/administração & dosagem
18.
Phytomedicine ; 64: 153082, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541796

RESUMO

BACKGROUND: Citrus flavonoids, consisting of naringin, narirutin, neohesperidine, etc., have therapeutic activities for the treatment of lipometabolic disorders. The peel of Citrus changshan-huyou (Qu Zhi Ke, QZK) is a new source of flavonoids, but attracted little attention so far. HYPOTHESIS: QZK should possess therapeutic effects against lipometabolic disorders due to the flavonoids it contains. STUDY DESIGN: In this study, we extracted and purified the flavonoids of QZK (TFCH) and established an obesity-induced non-alcoholic fatty liver disease (NAFLD) model of rats. TFCH was given orally for 8 weeks, and its anti-NAFLD effects and potential mechanism were evaluated. METHODS: The flavonoid chemoprofile of TFCH was determined by using HPLC. High-fat diet was employed to induce NAFLD model in rats, and six groups were set up: negative control group, reference treatment group, model group, low-dose TFCH (25 mg/kg), intermediate-dose TFCH (50 mg/kg), and high-dose TFCH (100 mg/kg). Serum and liver levels of inflammatory cytokines and NAFLD markers were measured biochemically. The relative mRNA expressions of liver T-bet, GATA3, and TNF-α were tested by real time PCR (qPCR) analysis. The protein expression of p38 and the phosphorylation of NF-κB, ERK1/2, and p38 in liver were tested by Western blot analysis. RESULTS: The histopathological observation showed that TFCH attenuated hepatic lesions with significantly decreased NAFLD activity scores. The biochemical data showed that TFCH significantly suppressed both systemic and intrahepatic inflammation by inhibiting IL-1ß, IL-6, IL-12, TNF-α, and IFN-γ, and the qPCR analysis revealed a Th1/Th2 related anti-inflammatory mechanism of TFCH. Western blot results clarified that TFCH exerted hepatoprotective and anti-inflammatory effects by suppression of phosphorylated NF-κB and MAPKs, indicating a mechanism associated with NF-κB and MAPK signaling pathways. CONCLUSION: QZK is a new source of Citrus flavonoids for therapeutic use, and TFCH is a promising representative of Citrus flavonoids for anti-NAFLD therapy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citrus/química , Flavonoides/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Substâncias Protetoras/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Dieta Hiperlipídica/efeitos adversos , Flavonoides/química , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Substâncias Protetoras/química , Ratos Sprague-Dawley
19.
World J Gastroenterol ; 25(33): 4814-4834, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31543676

RESUMO

The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis. The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis. In this mutual relationship, the liver acts as a second firewall towards potentially harmful substances translocated from the gut, and is, in turn, is implicated in the regulation of the barrier. Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage. In particular, in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment, diet and gut dysbiosis as the primary pathogenic trigger. In advanced liver disease, intestinal permeability is enhanced by portal hypertension. The clinical consequence is an increased bacterial translocation that further worsens liver damage. Furthermore, this pathogenic mechanism is implicated in most of liver cirrhosis complications, such as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, and hepatocellular carcinoma. After liver transplantation, the decrease in portal pressure should determine beneficial effects on the gut-liver axis, although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking. How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area, which deserves further attention.


Assuntos
Hipertensão Portal/etiologia , Mucosa Intestinal/metabolismo , Cirrose Hepática/etiologia , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica/etiologia , Translocação Bacteriana , Progressão da Doença , Disbiose/complicações , Disbiose/patologia , Humanos , Hipertensão Portal/patologia , Hipertensão Portal/cirurgia , Mucosa Intestinal/patologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Hepatopatia Gordurosa não Alcoólica/patologia , Permeabilidade , Resultado do Tratamento
20.
World J Gastroenterol ; 25(33): 4904-4920, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31543682

RESUMO

BACKGROUND: The trans-fat containing AMLN (amylin liver non-alcoholic steatohepatitis, NASH) diet has been extensively validated in C57BL/6J mice with or without the Lepob/Lepob (ob/ob) mutation in the leptin gene for reliably inducing metabolic and liver histopathological changes recapitulating hallmarks of NASH. Due to a recent ban on trans-fats as food additive, there is a marked need for developing a new diet capable of promoting a compatible level of disease in ob/ob and C57BL/6J mice. AIM: To develop a biopsy-confirmed mouse model of NASH based on an obesogenic diet with trans-fat substituted by saturated fat. METHODS: Male ob/ob mice were fed AMLN diet or a modified AMLN diet with trans-fat (Primex shortening) substituted by equivalent amounts of palm oil [Gubra amylin NASH, (GAN) diet] for 8, 12 and 16 wk. C57BL/6J mice were fed the same diets for 28 wk. AMLN and GAN diets had similar caloric content (40% fat kcal), fructose (22%) and cholesterol (2%) level. RESULTS: The GAN diet was more obesogenic compared to the AMLN diet and impaired glucose tolerance. Biopsy-confirmed steatosis, lobular inflammation, hepatocyte ballooning, fibrotic liver lesions and hepatic transcriptome changes were similar in ob/ob mice fed the GAN or AMLN diet. C57BL/6J mice developed a mild to moderate fibrotic NASH phenotype when fed the same diets. CONCLUSION: Substitution of Primex with palm oil promotes a similar phenotype of biopsy-confirmed NASH in ob/ob and C57BL/6J mice, making GAN diet-induced obese mouse models suitable for characterizing novel NASH treatments.


Assuntos
Modelos Animais de Doenças , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Óleo de Palmeira/efeitos adversos , Animais , Biópsia , Dieta Hiperlipídica/efeitos adversos , Humanos , Leptina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Hepatopatia Gordurosa não Alcoólica/patologia , Ácidos Graxos Trans/efeitos adversos
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