View clinical trials related to Fatty Liver.
Filter by:Dithiolethiones, a novel class of adenosine monophosphate-activated protein kinase (AMPK) activators, prevent insulin resistance through AMPK-dependent p70 ribosomal S6 kinase-1 (S6K1) inhibition. And it is well known that the modulation of S6K1 by oltipraz inhibited the development of insulin resistance and hyperglycemia through the AMPK-S6K1 pathway.Also some research reported that LXRg (a member of the nuclear hormone receptor)-mediated increases in SREBP-1c (the sterol regulatory element-binding protein-1c gene) promote the expression of lipogenic genes and enhance fatty acid synthesis and oltipraz inhibits LXRg and SREBP-c. Therefore, Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.
The purpose of this study is to understand why Hispanics who are overweight have a higher incidence of fatty liver disease.
Within large number of patients with obesity, it is crucial to determine who is at the greatest risk for development of chronic heart disease. The investigators previous studies suggest that an excessive accumulation of fat in heart cells precedes the development of obesity-related pathologies and may serve as a biomarker of heart disease in high-risk population. Until now, the evaluation of fat in the human heart was possible postmortem or by biopsy. The investigators novel magnetic resonance spectroscopy technique enables the quantification of intracellular lipid content non-invasively and repeatedly in humans in vivo. It could be used to better screen and treat obese patients at risk for the development of metabolic disease. The investigators hypothesize that in obese humans with elevated myocardial triglycerides, treatment with Nebivolol will reduce myocardial fat and will improve heart function.
The objective of this study is to investigate the potential beneficial effect of increasing protein in the diet in order to decrease hepatic lipid accumulation on a high-fat diet. The investigators hypothesize that increasing protein in a high-fat diet suppresses lipid accumulation in the liver, and that changes in (hepatic) fat handling underlie this reduced lipid accumulation.
The central hypothesis of this proposal is that a reduction in hepatic mitochondrial function is the main pathophysiology behind NAFLD (Non-Alcoholic Fatty Liver Disease) and NASH (Non alcoholic steatohepatitis). The investigators further hypothesize that lifestyle modifications through aerobic exercise training without weight loss or diet-induced weight loss are effective in reducing NAFLD parameters by improving hepatic mitochondrial content and function in human subjects. The investigators propose a randomized, controlled human clinical trial to compare the effects of aerobic exercise training (without weight loss) versus diet-induced weight loss (without exercise) in individuals who have NAFLD or liver biopsy-confirmed NASH
The incidence of Non alcoholic fatty liver disease (NAFLD) continues to increase, and prevalence estimates for NAFLD range from 17-33%, making it is the most common cause of chronic liver disease in North America. It is associated with increased cardiovascular morbidity as well as progression to cirrhosis is a subset of patients. There is currently no approved treatment for NAFLD. A key barrier to the development of effective therapies is a lack of consensus on the criteria for diagnosis and endpoints for studies evaluating diagnostic markers, prognosis and therapeutic modalities. NAFLD encompasses an entire pathological spectrum of disease, from relatively benign accumulation of lipid (steatosis) to progressive non alcoholic steatohepatitis (NASH) associated with inflammation, fibrosis, and necrosis. It has been estimated that 20-30% of patients with NAFLD will exhibit biochemical and histological changes characteristic of NASH, and 15-20% of those patients will progress to have cirrhosis. NASH remains an important phenotypic state, because this sub-group of patients is deemed at high-risk for developing progressive disease resulting in cirrhosis, liver failure requiring transplantation, or death. Although NAFLD has not to date been included as a component of the metabolic syndrome, there is increasing evidence that NAFLD frequently accompanies the development of insulin resistance and therefore may be an indicator or predictor of future cardiometabolic risk. Moreover, recent findings in skeletal muscle of experimental insulin resistance (lipid infusion) as well as naturally occurring obese and type 2 diabetic, insulin resistant patients show that skeletal muscle inflammation leads to a pattern of extracellular matrix, structural, and remodeling abnormalities that closely resemble the TGFb, connective tissue growth factor (CTGF) mediated fibrotic response that differentiates simple steatotic liver from NASH. This suggests there may be a common underlying mechanism. Given the ready availability of skeletal muscle tissue using percutaneous needle muscle biopsies, compared to the more invasive liver biopsy, it may be possible to use characteristics of skeletal muscle to distinguish the severity of liver fibrosis. Given the preponderance of patients being identified with NAFLD, the recognition of less and non invasive tests that help to discriminate the different phenotypic types of NAFLD would be highly practical and useful. This would help identify patients at risk of progression to cirrhosis, and thus make them the target of any available therapeutic interventions. The investigators hypothesize that 1. Insulin resistance measured through glucose tolerance test directly correlates with the extent of liver and muscle fibrosis, and 2. Inflammation and fibrosis in the skeletal muscles correlates with the histopathological changes seen in patients with NAFLD, and potentially skeletal muscle inflammation may be used as a diagnostic predictor to differentiate patients with NASH from patients with simple steatosis. The overall goal of this project is to determine the extent to which inflammation and fibrosis in skeletal muscle mirrors and is predictive of the level of liver inflammation and can distinguish NASH from simple steatosis. Specifically, the investigators propose the following Aims: 1. To use estimates of insulin sensitivity from modeling of oral glucose tolerance tests to test the hypothesis that the extent of liver and muscle fibrosis is directly related to insulin resistance. 2. To use liver and muscle biopsies to characterize the changes in abundance of mRNAs and proteins that characterize inflammation, extracellular matrix remodeling, and fibrosis. The investigators will use quantitative rt-PCR and immunoblot analysis to compare mRNA expression and protein abundance of collagens I and III, fibronectin, and connective tissue growth factor (CTGF) to test the hypothesis that there is a direct relationship between the levels of these proteins in muscle and liver and the degree of fibrosis. 3. To establish a biospecimen repository of serum, mRNA from circulating white blood cells, liver and muscle tissue, and DNA to serve as the substrate for future studies of the pathogenesis of NASH.
Due to the western lifestyle, correlated with a high calorie intake and low physical activity, obesity is becoming a major health problem. All over the world obesity reaches epidemic proportions. Obesity is closely linked to type 2 diabetes, a multi-factorial disease that increases the presence of multiple health problems. Until now, exercise and dietary intervention seem to be the single most effective interventions to treat obesity and type 2 diabetes mellitus. In obesity and type 2 diabetes, not only fat accumulation in adipose tissue, but also fat accumulation in the peripheral tissues occurs. Fat accumulation in peripheral tissues has been associated with insulin resistance. Exercise seems to have a positive effect on the accumulation of fat in the peripheral tissue and on the insulin sensitivity in type 2 diabetic patients. In this study we want to investigate if a prolonged exercise training program can lower the intrahepatic lipid content and can improve the metabolism of the liver in type 2 diabetic patients and patients with non-alcoholic fatty liver disease, and to examine if this leads to improvements in metabolic risk markers. To this end, we will include investigation of the effect of exercise on adipose tissue (inflammatory markers and adipocyte size) and skeletal muscle (ex vivo lipid metabolism) to incorporate the effect of exercise on liver, muscle and adipose tissue and to clarify the crosstalk between these tissues in the pathophysiology of type 2 diabetes.
Over the past 30 years, the prevalence of childhood obesity in the United States has tripled from 5% to 15%. Major consequences of obesity include insulin resistance, type- 2 diabetes, cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). The liver pathology encompasses a range from isolated fatty liver to advanced fibrosis, cirrhosis and end-stage liver disease. Weight loss, particularly if gradual, may lead to improvement in liver histology. Unfortunately, few patients in the pediatric population are willing to follow these recommendations and achieve weight loss. Medical treatment directed specifically at the liver disease has only recently been investigated and approved in patients with NAFLD. The beneficial effects of fish oil are attributed to its high concentrations of n - 3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are major regulators of pathways that participate in decreased production and break down of triglycerides and fatty acids in the liver. The investigators hypothesize that children with obesity related NAFLD will normalize elevated liver enzymes, plasma lipid levels, and attenuate insulin resistance with supplements of n-3 fatty acids. If this hypothesis is proven true, then fish oil could be used to treat NAFLD and to prevent the deterioration of fatty liver into end-stage liver disease.
The purpose of this study is to evaluate the effect of GWP42003 on liver triglyceride (liver fat) in participants with fatty liver disease (FLD).
This is a Phase I/II open-label uncontrolled, prospective study to assess the clinical and biological effects of Deferasirox (ICL 670, Exjade®) in patients with NASH and increased iron storage / distribution of iron on liver function and liver histology. NASH is defined clinically and histologically by elevated liver enzymes, signs of hepatic steatosis on ultrasound and magnetic resonance imaging, impaired liver function as expressed by functional breath tests, and significantly altered liver histology. Patients will be treated in a phase I and phase II part for either 12 or 48 weeks. Both study parts have different endpoints: in phase I the side effect profile will be evaluated while in phase II the therapeutic response will be tested. Accordingly, measures will be different. Approximately 10 patients in phase I and 50 patients in phase II will be enrolled according to sample size calculations. The design is an "adaptive" Two-stage design, allowing to minimize the number of patients included into the trial as well as to introduce corrections for the second stage.