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1.
Nutr Metab Cardiovasc Dis ; 31(4): 1308-1316, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33618924

RESUMO

BACKGROUND AND AIMS: The relationship between insulin resistance (IR) and hepatic steatosis (fatty liver) is well known; however, the extent to which the satiety hormone leptin acts as a confounder or mediator in this relationship is uncertain. We examined whether the association between IR and hepatic steatosis is mediated by leptin in Colombian adolescents with excess adiposity. METHODS AND RESULTS: A total of 122 adolescents (mean age: 13.4 years; 68% girls) participated in the study. We assessed body composition, hepatic steatosis (as defined by the controlled attenuation parameter [CAP]), cardiometabolic risk factors (body mass index, waist circumference, body composition), biochemical variables (leptin, insulin, glucose, lipid profile, cardiometabolic Z-score, transaminases, etc.), and physical fitness (cardiorespiratory fitness and grip strength). Partial correlation, regression, and mediation analyses were conducted using the Barron and Kenny framework. RESULTS: Ninety-two youths (75.4%) had IR. Mediation analysis revealed a positive relationship between Homeostasis Model Assessment-IR (HOMA-IR) and CAP (ßdir = 3.414, 95% confidence interval [CI]: 1.012 to 5.816, p < 0.001), which was attenuated when leptin was included in the model, thus indicating that leptin mediates this relationship (ßind = 1.074, 95% CI: 0.349 to 2.686, p < 0.001). The percentage of the total effect mediated by leptin was 21%. Regarding sex, the mediation effect of leptin remains significant among boys (ßind = 0.962, 95% CI: 0.009 to 2.615, p < 0.001), but not in girls (ßind = 0.991, 95% CI: 1.263 to 5.483, p = 0.477). CONCLUSIONS: The findings are clinically relevant to consider leptin levels as a surrogate marker of insulin sensitivity when assessing youths with excess adiposity and/or suspected Nonalcoholic hepatic steatosis or nonalcoholic fatty liver disease (NAFLD).


Assuntos
Adiposidade , Resistência à Insulina , Leptina/sangue , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade Pediátrica/sangue , Adolescente , Fatores Etários , Biomarcadores/sangue , Criança , Colômbia , Estudos Transversais , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade Pediátrica/complicações , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/fisiopatologia , Medição de Risco , Fatores de Risco
2.
Isr Med Assoc J ; 23(2): 94-98, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33595214

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is emerging as an important public health condition. The effect of Ramadan fasting on several metabolic conditions has been previously assessed. OBJECTIVES: To assess the impact of Ramadan fasting on non-alcoholic steatohepatitis (NASH) severity scores. METHODS: A retrospective, case control study was conducted in Nazareth Hospital between 2017 and 2019. We included NAFLD patients who had been diagnosed by abdominal ultrasonography. The study population was divided in two matched groups: NASH subjects who fasted all of Ramadan and NAFLD/NASH subjects who did not fast (control). Metabolic/NASH severity scores, homeostatic model assessment of ß-cell function and insulin resistance (HOMA-IR), NAFLD Fibrosis Score (NFS), BARD scores, and fibrosis-4 (FIB4) scores were assessed in both groups before and after the Ramadan month. RESULTS: The study included 155 NASH subjects, 74 who fasted and 81 who did not. Among the fasting group, body mass index decreased from 36.7 ± 7.1 to 34.5 ± 6.8 after fasting (P < 0.003), NFS declined from 0.45 ± 0.25 to 0.23 ± 0.21 (P < 0.005), BARD scores declined from 2.3 ± 0.98 to 1.6 ± 1.01 (P < 0.005), and FIB4 scores declined from 1.93 ± 0.76 to 1.34 ± 0.871 (P < 0.005). C-reactive protein decreased from 14.2 ± 7.1 to 7.18 ± 6.45 (P < 0.005). Moreover, HOMA-IR improved from 2.92 ± 1.22 to 2.15 ± 1.13 (P < 0.005). CONCLUSIONS: Ramadan fasting improved on inflammatory markers, insulin sensitivity, and noninvasive measures for NASH severity assessment.


Assuntos
Jejum/fisiologia , Resistência à Insulina/fisiologia , Islamismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Adulto , Idoso , Biomarcadores/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
3.
Food Funct ; 12(5): 2171-2188, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33566044

RESUMO

The present study was designed to explore the beneficial mitochondrial effects and anti-oxidative activities of plant sterol ester of α-linolenic acid (PS-ALA) through AMP-activated protein kinase (AMPK) signaling in the treatment of nonalcoholic fatty liver disease (NAFLD) using in vivo and in vitro models. The mitochondrial function was evaluated and the oxidative stress index was measured. The protein expression was analyzed by immunohistochemical, immunofluorescence, and western blotting methods. The results showed that PS-ALA significantly suppressed NAFLD and alleviated steatosis in HepG2 cells induced by oleic acid (OA). In addition, PS-ALA promoted mitochondrial biogenesis, enhanced mitochondrial fatty acid oxidation capacity, improved mitochondrial dynamics, and restored mitochondrial membrane potential. Moreover, PS-ALA reduced reactive oxygen species production both in the liver tissue of HFD-fed mice and OA-loaded HepG2 cells. At the molecular level, PS-ALA accelerated the phosphorylation of AMPK and increased the protein expression of peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and nuclear NF-E2-related factor 2 (Nrf2). Furthermore, the stimulating effects of PS-ALA on the PGC-1α/Nrf1/Tfam pathway and Nrf2/HO-1 pathway as well as its mitochondrial biogenesis promotion effects and anti-oxidative activities were abrogated by the AMPK inhibitor in OA-treated HepG2 cells. In conclusion, the protective effects of PS-ALA on NAFLD appear to be associated with improving mitochondrial function and oxidative stress via activating AMPK signaling.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ésteres/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fitosteróis/uso terapêutico , Ácido alfa-Linoleico/química , Animais , Dieta Hiperlipídica , Ativação Enzimática/efeitos dos fármacos , Ésteres/química , Células Hep G2 , Humanos , Fígado/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/fisiologia , Mitocôndrias Hepáticas/ultraestrutura , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Fosforilação , Fitosteróis/química , Espécies Reativas de Oxigênio/análise , Transdução de Sinais/efeitos dos fármacos
4.
Life Sci ; 271: 119220, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33592199

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a disorder of excessive fat accumulation in the liver, known as steatosis, without alcohol overconsumption. NAFLD can either manifest as simple steatosis or steatohepatitis, known as non-alcoholic steatohepatitis (NASH), which is accompanied by inflammation and possibly fibrosis. Furthermore, NASH might progress to hepatocellular carcinoma. NAFLD and NASH prevalence is in a continuous state of growth, and by 2018, NAFLD became a devastating metabolic disease with a global pandemic prevalence. The pathophysiology of NAFLD and NASH is not fully elucidated, but is known to involve the complex interplay between different metabolic, environmental, and genetic factors. In addition, unhealthy dietary habits and pre-existing metabolic disturbances together with other risk factors predispose NAFLD development and progression from simple steatosis to steatohepatitis, and eventually to fibrosis. Despite their growing worldwide prevalence, to date, there is no FDA-approved treatment for NAFLD and NASH. Several off-label medications are used to target disease risk factors such as obesity and insulin resistance, and some medications are used for their hepatoprotective effects. Unfortunately, currently used medications are not sufficiently effective, and research is ongoing to investigate the beneficial effects of different drugs and phytochemicals in NASH. In this review article, we outline the different risk factors and pathophysiological mechanisms involved in NAFLD, diagnostic procedures, and currently used management techniques.


Assuntos
Fígado/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/terapia , Curcumina/farmacologia , Curcumina/uso terapêutico , Humanos , Resistência à Insulina/fisiologia , Fígado/efeitos dos fármacos , Transplante de Fígado/métodos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/terapia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade/diagnóstico , Obesidade/fisiopatologia , Obesidade/terapia , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Fatores de Risco
5.
Metabolism ; 117: 154708, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33444607

RESUMO

Nonalcoholic fatty liver disease (NAFLD) includes a broad spectrum of liver dysfunctions and it is predicted to become the primary cause of liver failure and hepatocellular carcinoma. Mitochondria are highly dynamic organelles involved in multiple metabolic/bioenergetic pathways in the liver. Emerging evidence outlined that hepatic mitochondria adapt in number and functionality in response to external cues, as high caloric intake and obesity, by modulating mitochondrial biogenesis, and maladaptive mitochondrial response has been described from the early stages of NAFLD. Indeed, mitochondrial plasticity is lost in progressive NAFLD and these organelles may assume an aberrant phenotype to drive or contribute to hepatocarcinogenesis. Severe alimentary regimen and physical exercise represent the cornerstone for NAFLD care, although the low patients' compliance is urging towards the discovery of novel pharmacological treatments. Mitochondrial-targeted drugs aimed to recover mitochondrial lifecycle and to modulate oxidative stress are becoming attractive molecules to be potentially introduced for NAFLD management. Although the path guiding the switch from bench to bedside remains tortuous, the study of mitochondrial dynamics is providing intriguing perspectives for future NAFLD healthcare.


Assuntos
Mitocôndrias/fisiologia , Dinâmica Mitocondrial/fisiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Animais , Carcinoma Hepatocelular/fisiopatologia , Humanos , Fígado/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , Estresse Oxidativo/fisiologia
6.
J Agric Food Chem ; 69(2): 655-667, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33404223

RESUMO

Nonalcoholic steatohepatitis (NASH) is an inflammatory lipotoxic disorder characterized by lipid accumulation and inflammation. Diosmetin (Dios), a flavonoid, has an active effect against nonalcoholic fatty liver disease, whereas its effect on NASH remains elusive. To investigate the effects of Dios on lipogenesis and inflammatory response and explore the molecular mechanisms of Dios on NASH, mice induced by high-fat diet (HFD), HepG2 cells stimulated by palmitic acid (PA), transcriptome sequencing, and molecular biological experiments were used. We show, by pathological analysis (HE, Oli Red O, and Masson staining) and biochemical parameters (TC, TG, LDL-C, ALT, and AST), Dios alleviated liver lipid accumulation and inflammatory injury. According to liver RNA-Seq analysis, CXCL10 and STAT1 were assumed to be the key target genes of Dios on NASH. Significantly, Dios regulated STAT1/CXCL10 signal pathway and further attenuated NASH via regulating the expression of LXRα/ß, SREBP-1c, CHREBP, and NF-κB. In conclusion, Dios is proposed to alleviate NASH through suppression of lipogenesis and inflammatory response via a STAT1/CXCL10-dependent pathway.


Assuntos
Quimiocina CXCL10/imunologia , Flavonoides/administração & dosagem , Lipogênese/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fator de Transcrição STAT1/imunologia , Animais , Quimiocina CXCL10/genética , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Fator de Transcrição STAT1/genética , Transdução de Sinais/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/imunologia
7.
Arq Bras Cir Dig ; 33(3): e1549, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33470379

RESUMO

BACKGROUND: Strongly associated with obesity, non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome. It presents as simple steatosis and steatohepatitis, which can progress to cirrhosis and its complications. Among the therapeutic alternatives is bariatric surgery. AIM: To compare the effect of the two most frequent bariatric procedures (sleeve and bypass) on liver disease regarding to epidemiological, demographic, clinical and laboratory parameters. METHODS: The results of intraoperative and 12 months after surgery liver biopsies were used. The NAFLD activity score (NAS) was used to assess and compare the stages of liver disease. RESULTS: Sixteen (66.7%) patients underwent Bypass procedure and eight (33.3%) Sleeve. It was observed that the variation in the NAFLD activity score was significantly greater in the Bypass group than in Sleeve (p=0.028) and there was a trend regarding the variation in fibrosis (p=0.054). CONCLUSION: Both surgical techniques were effective in improving the hepatic histology of most operated patients. When comparing sleeve and bypass groups, bypass showed better results, according to the NAS score.


Assuntos
Cirurgia Bariátrica/métodos , Derivação Gástrica/métodos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade Mórbida/cirurgia , Perda de Peso , Adulto , Biópsia , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Obesidade Mórbida/complicações , Fatores de Risco , Resultado do Tratamento
8.
Life Sci ; 270: 119135, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33513397

RESUMO

Emerging studies have pointed to a significant relationship between exposure to ambient fine particulate matter (aerodynamic diameter < 2.5 µm, PM2.5) and the incidence of non-alcoholic fatty liver disease (NAFLD). By referring to previous studies on the pathogenesis of NAFLD and PM2.5 exposure-induced metabolic damage, we summarized the possible mediating pathways through which PM2.5 exposure can cause the phenotype and progression of NAFLD. Crucially, PM2.5 exposure is considered to have an impact on the classic hypothesis "multiple hits" of NAFLD. In addition, we also concluded that exposure to PM2.5 can promote the development of NAFLD by destroying the intestinal epithelium and microbiotic homeostasis, triggering endoplasmic reticulum stress, inducing abnormal expression of specific microRNA or inflammatory factors.


Assuntos
Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Material Particulado/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo
10.
Medicine (Baltimore) ; 99(50): e23619, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327335

RESUMO

Over half of metabolic syndrome (MetS) patients have nonalcoholic fatty liver disease (NAFLD). To prevent its complications, standard routine screening is required, but the human-resource and budgetary implications need to be taken into consideration. This study compared the performances of 4 noninvasive scoring systems in predicting NAFLD in MetS patients. They were the fatty liver index, hepatic steatosis index, lipid accumulation product index, and nonalcoholic fatty liver disease in metabolic syndrome patients scoring system (NAFLD-MS).Scores were determined for 499 MetS patients, including 249 patients in a type 2 diabetes mellitus (T2DM) subgroup. Ultrasonography was used to diagnose NAFLD. The accuracies and performance of the scoring systems were analyzed using published cutoff values, and comparisons were made of their areas under receiver operating characteristic curves, sensitivities, specificities, positive and negative predictive values, and likelihood ratios.NAFLD was detected in 68% of the MetS patients and 77% of the MetS patients with T2DM. According to the areas under receiver operating characteristic curves, fatty liver index and hepatic steatosis index provided better performances in predicting NAFLD. NAFLD-MS provided the highest specificity of 99% among the MetS patients as a whole, and it provided even better accuracy with similar performance when applied to the subgroup of MetS patients with T2DM. The maximum cost avoidance from unnecessary ultrasonography was also reported by using NAFLD-MS. In terms of simplicity and ease of calculation, the lipid accumulation product index and NAFLD-MS are preferred.All 4 scoring systems proved to be acceptable for predicting NAFLD among MetS and T2DM patients in settings where the availability of ultrasonography is limited. NAFLD-MS provided the highest specificity and cost avoidance, and it is simple to use. All 4 systems can help clinicians decide further investigations.


Assuntos
Testes de Função Hepática , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença
12.
Lancet Gastroenterol Hepatol ; 5(11): 996-1007, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32805205

RESUMO

BACKGROUND: The laxative drug lubiprostone improves intestinal permeability in healthy volunteers. We aimed to assess efficacy and safety of lubiprostone in patients with non-alcoholic fatty liver disease (NAFLD) with constipation via attenuation of intestinal permeability. METHODS: This randomised, double-blind, placebo-controlled, phase 2a study in Yokohama City University Hospital, Japan, recruited patients (aged 20-85 years) with NAFLD and constipation, alanine aminotransferase (ALT) at least 40 U/L, liver stiffness (≤6·7 kPa), and hepatic fat fraction at least 5·2% when assessed by MRI-proton density fat fraction. Eligible patients were randomly assigned (11:10:9) by a computer-based system and stratified by age and sex to receive 24 µg lubiprostone, 12 µg lubiprostone, or placebo, orally, once per day for 12 weeks. The primary endpoint was the absolute changes in ALT at 12 weeks. Efficacy analysis was done by intention to treat. Safety was assessed in all treated patients. This trial was registered with University Hospital Medical Information Network Clinical Trials Registry (UMIN000026635). FINDINGS: Between March 24, 2017, and April 3, 2018, we screened 288 patients, of whom 150 (52%) were randomly assigned to treatment: 55 patients were assigned to receive 24 µg lubiprostone, 50 to receive 12 µg lubiprostone, and 45 to receive placebo. A greater decrease in the absolute ALT levels from baseline to 12 weeks was seen in the 24 µg lubiprostone group (mean -13 U/L [SD 19]) than in the placebo group (1 U/L [24]; mean difference -15 U/L [95% CI -23 to -6], p=0·0007) and in the 12 µg lubiprostone group (-12 U/L [21]) than in the placebo group (mean difference -13 U/L [-22 to -5], p=0·0023). 18 (33%) of 55 patients in the 24 µg group had at least one adverse event, as did three (6%) of 47 patients in the 12 µg group and three (7%) of 43 in the placebo group. The most common adverse event was diarrhoea (17 [31%] of patients in the 24 µg group, three [6%] in the 12 µg group, none in the placebo group). No life-threatening events or treatment-related deaths occurred. INTERPRETATION: Lubiprostone was well tolerated and reduced the levels of liver enzymes in patients with NAFLD and constipation. Further studies are necessary to better define the efficacy and tolerability of lubiprostone in patients with NAFLD without constipation. FUNDING: Mylan EPD G.K.


Assuntos
Alanina Transaminase/sangue , Diarreia , Fígado , Lubiprostona , Hepatopatia Gordurosa não Alcoólica , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/etiologia , Diarreia/induzido quimicamente , Diarreia/diagnóstico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Laxantes/administração & dosagem , Laxantes/efeitos adversos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Testes de Função Hepática , Lubiprostona/administração & dosagem , Lubiprostona/efeitos adversos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Resultado do Tratamento
13.
PLoS One ; 15(8): e0237360, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845887

RESUMO

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has been associated with small bowel bacterial overgrowth (SIBO) and cardiometabolic dysfunction. This cross-sectional study aimed to evaluate the cardio-metabolic parameters and SIBO in patients with different degrees of hepatic fibrosis estimated by NAFLD fibrosis score (NFS). METHODS: Subjects (n = 78) were allocated to three groups: Healthy control (n = 30), NAFLD with low risk of advanced fibrosis (NAFLD-LRAF, n = 17) and NAFLD with a high risk of advanced fibrosis (NAFLD-HRAF, n = 31). Anthropometrics, blood pressure, electrocardiogram and heart rate variability (HRV) were evaluated. Only the NAFLD-LRAF and NAFLD-HRAF groups were submitted to blood biochemical analysis and glucose hydrogen breath tests. RESULTS: The NAFLD-HRAF group had higher age and body mass index when compared to the control and NAFLD-LRAF groups. The prevalence of SIBO in the NAFLD group was 8.33%. The low frequency/high-frequency ratio (LF/HF ratio) was augmented in NAFLD-LRAF (p < 0.05) when compared with control group. NAFLD-HRAF group had a wide QRS complex (p < 0.05) and reduced LF/HF ratio (p < 0.05) compared to the control and NAFLD-LRAF groups. Serum levels of albumin and platelets were more reduced in the NAFLD-HRAF subjects (p < 0.05) than in the NAFLD-LRAF. CONCLUSIONS: NAFLD impairs cardiac autonomic function. Greater impairment was found in subjects with a worse degree of hepatic fibrosis estimated by NFS. Hypoalbuminemia and thrombocytopenia were higher in subjects with a worse degree of hepatic fibrosis, whereas prevalence of SIBO positive was similar between the groups.


Assuntos
Bactérias/crescimento & desenvolvimento , Progressão da Doença , Intestinos/microbiologia , Miocárdio/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Eletrocardiografia , Feminino , Fibrose , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Risco
14.
Ann Endocrinol (Paris) ; 81(5): 493-499, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768394

RESUMO

The present study examined the effectiveness of adding exercises with whole-body vibration (WBV) to aerobic training in terms of metabolic features and quality of life. Patients with non-alcoholic fatty liver disease (NAFLD), confirmed on imaging, underwent an 8-week individualized exercise program randomized between aerobic training with and without WBV. Training was performed at 60-80% heart rate workload for 165 min/week. The WBV amplitude was 2-4mm and the training frequency was 30Hz, for 15min. Assessments were carried out on surrogate scores of steatosis and fibrosis including transient elastography (FibroScan), metabolic features (biochemical analysis) and quality of life (SF-36). Insulin resistance was markedly reduced (-2.36; 95% CI: -4.96 to -0.24; P: 0.049) in aerobic training with WBV. The decrease in serum aspartate transaminase was significantly greater in aerobic training without WBV (-14.81; 95% CI: -23.36 to -6.25; P: 0.029). There were no significant differences between groups for the other metabolic features (P<0.05). All quality of life well-being domains improved in both groups (P<0.05). Given this reduction in insulin resistance, WBV can usefully be added to aerobic training. However, WBV did not provide further benefits in improving metabolic properties or quality of life.


Assuntos
Terapia por Exercício/métodos , Hepatopatia Gordurosa não Alcoólica/terapia , Condicionamento Físico Humano/métodos , Qualidade de Vida , Vibração/uso terapêutico , Adulto , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/psicologia , Resultado do Tratamento
15.
Medicine (Baltimore) ; 99(32): e21568, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769900

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries, and strongly associated with type 2 diabetes mellitus (T2DM). Several studies have shown that hypoglycemic agents are effective for NAFLD combined with T2DM. However, there is still controversy over which hypoglycemic agent is the best for NAFLD combined with T2DM patients. OBJECTIVE: To systematically evaluate the efficacy and safety of hypoglycemic agents in NAFLD combined with T2DM patients. METHODS: A comprehensive electronic search will be conducted by searching Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Clinical Trials and Chinese Biomedical Medicine. All randomized controlled trials of hypoglycemic agents interventions for NAFLD combined with T2DM will be identified. Two reviewers independently screened and evaluated each included study and extracted the outcome indexes. ADDIS 1.16.8 software will be used for the network meta-analysis and STATA 14 software will be used for drawing network evidence plots and funnel plots. CONCLUSION: This network meta-analysis will provide stronger evidence for the efficacy and safety of hypoglycemic agents in the treatment of NAFLD combined with T2DM, and provide a reference for clinical application. PROTOCOL REGISTRATION NUMBER: INPLASY202070016.


Assuntos
Protocolos Clínicos , Hipoglicemiantes/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Metanálise como Assunto , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Revisões Sistemáticas como Assunto
16.
J Breath Res ; 14(4): 041002, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32663815

RESUMO

Fructose intake is associated with increased consumption of processed foods, specifically in the context of nutritional supplements. To assess gastrointestinal symptoms and hydrogen production after the ingestion of a fructose solution in runners, healthy and sick persons. Hydrogen test (H2 test) was performed after the intake a solution with 50 g fructose along with the application of a questionnaire to evaluate the gastrointestinal symptoms during the H2 test in three groups: Athletes group (AG); control group (CG) with healthy subjects; and non-alcoholic fatty liver disease group (NAFLDG). Statistical analysis was performed with analysis of variance at a p < 0.05 significance level. The AG was the largest H2 producer followed by the CG with significant difference between the AG and NAFLDG (p ≤ 0.05). Most participants remained asymptomatic, but the strongest correlation was the symptom of bloating GC (R = 0.625), eructation in NAFLD (R = 0.481) and diarrhea in CG (R = 0.345) and AG (R = 0.338) The result of the present study suggests the production of hydrogen by the colon following the administration of fructose is higher in athletes compared with healthy individuals and persons with NAFLD, showing that fructose intake may be an interesting point of dietary management, especially in elite professionals.


Assuntos
Frutose/química , Hidrogênio/química , Intestinos/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Corrida/fisiologia , Adulto , Feminino , Humanos , Masculino
17.
J Food Sci ; 85(7): 2198-2206, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32614078

RESUMO

The hemolytic property discourages the development of sea cucumber saponins on alleviating lipids metabolism disturbance. The hemolytic activity of saponins has been reported to be highly correlative to their chemical structures. The aim of this study was to reduce the hemolytic activity of sea cucumber-derived saponins echinoside A (EA) and simultaneously remain its effect on alleviating non-alcoholic fatty liver disease (NAFLD) by structural modifications. Administration with EA and its derivatives for 8 weeks remarkably mitigated orotic acid-induced NAFLD via inhibiting the activities and mRNA expressions of enzymes involved in lipogenesis, enhancing the activities and expressions of enzymes related to hepatic lipolysis in a rat model. Importantly, aglycone exhibited a distinct advantage in stimulating hepatic lipolysis compared with EA and dsEA, meanwhile possessed lowest hemolytic activity. This study may provide the theoretical basis to strengthen the application of sea cucumber saponins as food supplements and/or functional ingredients.


Assuntos
Holoturina/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Pepinos-do-Mar/química , Animais , Holoturina/administração & dosagem , Holoturina/química , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Ratos , Ratos Wistar , Saponinas/administração & dosagem , Saponinas/química
18.
Life Sci ; 257: 118090, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679144

RESUMO

AIMS: This study aimed to investigate oxymatrine via regulating miR-182 improved the hepatic lipid accumulation in non-alcoholic fatty liver disease (NAFLD) model. MATERIALS AND METHODS: Wistar rats were fed high-fat and high-fructose diet (HFDHFr group) for 4 weeks and HepG2 cells were treated with palmitic acid (PA group), and then were given oxymatrine intervention. The expression profiles of miRNAs were accessed by RNA sequencing (RNA-Seq). Hematoxylin-eosin (HE) staining and Oil Red O staining were used to observe the inflammation and lipid accumulation in liver. The levels of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty-acid synthase (FAS) and carnitine palmitoyltransferase 1A (CPT-1A) were detected by RT-qPCR and Western blotting, respectively. Cell viability was detected by Cell Counting Kit-8 (CCK-8). KEY FINDINGS: miR-182 was down-regulated in the HFDHFr group and PA group. Oxymatrine reduced body weight, and improved glucose tolerance and insulin resistance in the HFDHFr + OMT group compared with HFDHFr group. In addition, oxymatrine reduced the ratio (liver weight/body weight), the content of triglycerides (TG), hepatic lipid accumulation and steatosis. The levels of SREBP-1c, ACC, and FAS were significantly decreased, while the CPT-1A level was obviously elevated after oxymatrine intervention (P < 0.05). In vivo, miR-182 knockdown increased the levels of SREBP-1c, ACC and FAS, while reduced the CPT-1A level. Additionally, oxymatrine attenuated the effects of miR-182 inhibitor on lipid accumulation. SIGNIFICANCE: We presented a possible mechanism that oxymatrine alleviated hepatic lipid metabolism via regulating miR-182 in NAFLD model.


Assuntos
Alcaloides/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Quinolizinas/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Ácido Palmítico/administração & dosagem , Ratos , Ratos Wistar
19.
Arch Endocrinol Metab ; 64(3): 235-242, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555989

RESUMO

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The aims of this study were to investigate the prevalence and factors associated with NAFLD in women with PCOS and evaluate noninvasive indices of hepatic fibrosis in patients with PCOS and NAFLD. SUBJECTS AND METHODS: Patients with PCOS (n = 87) and women without PCOS (n = 40; controls) were included. NAFLD was diagnosed by abdominal ultrasonography after exclusion of alcohol consumption and viral or autoimmune liver disease. Anthropometric, clinical and metabolic variables, homeostasis model assessment of insulin resistance (HOMA-IR) index, lipid accumulation product (LAP), FIB-4 index, NAFLD score, and transient elastography (TE; FibroScan) were obtained in subsets of patients with PCOS and NAFLD. RESULTS: A total of 87 patients with PCOS were included (mean age: 34.4 ± 5.7 years, mean body mass index [BMI]: 34.7 ± 4.7 kg/m 2 ). NAFLD was present in 67 (77.0%) patients with PCOS versus 21 of 40 (52.5%) controls (p = 0.005). Women with PCOS and liver steatosis, compared with their NAFLD-free counterparts, had higher values of BMI, waist circumference, triglycerides, total cholesterol, alanine and aspartate aminotransferases, and γ-glutamyltransferase, along with higher frequencies of obesity, metabolic syndrome, and insulin resistance. NAFLD was independently associated with waist circumference, serum triglycerides, and alanine aminotransferase levels. The FIB-4 index was not compatible with advanced fibrosis in any of the evaluated patients, while NAFLD score and TE were compatible with advanced liver fibrosis in 1 of 26 (3.8%) and 3 of 25 (12%) patients, respectively. CONCLUSION: Women with PCOS had a high risk of NAFLD, and a combination of both was associated with central obesity, dyslipidemia, insulin resistance, and metabolic syndrome. Noninvasive methods suggested low rates of severe hepatic fibrosis in Brazilian women with PCOS. Arch Endocrinol Metab. 2020;64(3):235-42.


Assuntos
Hepatopatia Gordurosa não Alcoólica/etiologia , Síndrome do Ovário Policístico/complicações , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Resistência à Insulina , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Síndrome do Ovário Policístico/fisiopatologia , Fatores de Risco , Circunferência da Cintura
20.
Medicine (Baltimore) ; 99(26): e20898, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590801

RESUMO

This study was performed to explore the relationship between coronary heart disease (CHD) and nonalcoholic fatty liver disease (NAFLD) in patients without hypertension and diabetes with a focus on predicting CHD.In total, 78 consecutive patients without hypertension and diabetes who were suspected of CHD underwent coronary angiography (CAG) or computed tomography CAG. They were segregated into the CHD and non-CHD group according to the CAG or computed tomography angiography results. The Gensini score was calculated based on CAG results in the CHD group. All patients underwent ultrasonographic measurement of the liver, subcutaneous fat, and visceral fat thickness.The CHD and the Gensini score were significantly correlated with V1, V2, and NAFLD. As the grade of NAFLD increases, the Gensini score was increased. After correcting for confounding factors, NAFLD (B = 2.474, P < .001, 95% confidence interval: 3.32-42.406) and cholesterol (B = 1.176, P = 0.025, 95% confidence interval: 1.155-9.101) were predictor for CHD.The CHD is associated with NAFLD in the patients without hypertension and diabetes. The high-grade NAFLD may be predicted the risk of CHD in patients without hypertension and diabetes.


Assuntos
Doença das Coronárias/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia , Adulto , Idoso , China/epidemiologia , Doença das Coronárias/epidemiologia , Doença das Coronárias/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Ultrassonografia/métodos
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