Models for Non-Alcoholic Fatty Liver Disease: A Link with Vascular Risk

Xirouchakis, Elias; Sigalas, A; Manousou, Pinelopi; Calvaruso, Vincenza; Pleguezuelo, M.; Corbani, A; Maimone, S.; Patch, D.; Burroughs, AK

doi:10.2174/138161208783497705

Cited by 8 publications

(3 citation statements)

References 71 publications

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“…Hepatic steatosis also increases the risk for CVD [ 13 , 15 ] leading to endothelial dysfunction, atherosclerosis and hypertension [ 14 , 61 , 62 ]. Non-alcoholic fatty liver might contribute in the pathogenesis of CVD through the systemic release of inflammatory and oxidative-stress mediators or through the contribution of hepatic steatosis to insulin resistance and atherogenic dyslipidemia.…”

Section: Discussionmentioning

confidence: 99%

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet

et al. 2015

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BackgroundOxidative stress underlies the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), obesity and cardiovascular disease (CVD). Heme Oxygenase-1 (HO-1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1) belongs to the family of NAD-dependent de-acyetylases and is modulated by cellular redox.HypothesisWe hypothesize that fructose-induced obesity creates an inflammatory and oxidative environment conducive to the development of NAFLD and metabolic syndrome. The aim of this study is to determine whether HO-1 acts through SIRT1 to form a functional module within hepatocytes to attenuate steatohepatitis, hepatic fibrosis and cardiovascular dysfunction.Methods and ResultsWe examined the effect of fructose, on hepatocyte lipid accumulation and fibrosis in murine hepatocytes and in mice fed a high fructose diet in the presence and absence of CoPP, an inducer of HO-1, and SnMP, an inhibitor of HO activity. Fructose increased oxidative stress markers and decreased HO-1 and SIRT1 levels in hepatocytes (p<0.05). Further fructose supplementation increased FAS, PPARα, pAMPK and triglycerides levels; CoPP negated this increase. Concurrent treatment with CoPP and SIRT1 siRNA in hepatocytes increased FAS, PPARα, pAMPK and triglycerides levels suggesting that HO-1 is upstream of SIRT1 and suppression of SIRT1 attenuates the beneficial effects of HO-1. A high fructose diet increased insulin resistance, blood pressure, markers of oxidative stress and lipogenesis along with fibrotic markers in mice (p<0.05). Increased levels of HO-1 increased SIRT1 levels and ameliorated fructose-mediated lipid accumulation and fibrosis in liver along with decreasing vascular dysfunction (p<0.05 vs. fructose). These beneficial effects of CoPP were reversed by SnMP.ConclusionTaken together, our study demonstrates, for the first time, that HO-1 induction attenuates fructose-induced hepatic lipid deposition, prevents the development of hepatic fibrosis and abates NAFLD-associated vascular dysfunction; effects that are mediated by activation of SIRT1 gene expression.

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Section: Discussionmentioning

confidence: 99%

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet

et al. 2015

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“…cirrhosis) was present in 20% of these diabetics. Since nearly half of the patients with NASH die of cardiovascular disease and malignancy [51, 52], NASH may thus be overlooked or underdiagnosed at the initial stage of diagnosis. As biopsy may not be a practical diagnostic test for all suspected fatty liver diseases, alternative noninvasive tests that are cheaper and easier predictors of NAFLD in large populations are needed.…”

Section: Us Perspectivesmentioning

confidence: 99%

Global Epidemiology of Nonalcoholic Fatty Liver Disease and Perspectives on US Minority Populations

et al. 2016

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Non-alcoholic fatty liver disease (NAFLD), a clinical syndrome that is predicted to affect millions of people worldwide, will become the next global epidemic. The natural course of this disease, including its subtype, non-alcoholic steatohepatitis (NASH), is not clearly defined, especially in the US minority populations. The aim of this review is to report the global epidemiology of NAFLD, with emphasis on US minority populations on the basis of database searches using using Pubmed and other online databases. The US Hispanic population is the most disproportionately affected ethnic group with hepatic steatosis whereas African-Americans are the least affected. Genetic disparities involved in lipid metabolism seem to be the leading explanation for the lowest incidence and prevalence of both NAFLD and NASH in African-Americans.

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“…Unfortunately, fatty liver disease likely has even farther reaching human health implications. Simple hepatic macrosteatosis (HMS), defined as macrosteatosis regardless of inflammation, ballooning, or fibrosis, has been linked to insulin resistance, obesity, hyperlipidemia [6], and atherosclerotic heart disease in humans [6, 7]. Currently, human clinical investigation of hepatic steatosis and its response to therapy is limited by dependence upon liver biopsy, an invasive and sometimes unpleasant procedure that carries a very small risk of serious complication [8].…”

Section: Introductionmentioning

confidence: 99%

Non-contrasted Computed Tomography for the Accurate Measurement of Liver Steatosis in Obese Patients

et al. 2011

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BackgroundHepatic macrosteatosis (HMS) is prevalent among high BMI patients, but a lack of validation of non-invasive measures of liver fat hampers non-alcoholic liver disease (NAFLD) investigation in general. Recent work suggests BMI adjusted, non-contrasted computed tomography (nc-CT) attenuation data (Hounsfield units) reflects liver fat accumulation in a normal weight population. However, this and other CT-based HMS studies have only approximated macrosteatosis (%) histologically, but have not validated findings with chemical liver triglyceride (TG) concentrations (mg/gram protein). Also, all previous CT based steatosis studies excluded high BMI subjects, whose habitus may affect properties of the scan. We hypothesized that in high BMI patients nc-CT attenuation measurements expressed in Hounsfield units (HU) accurately estimate liver triglyceride concentrations as well as histological macrosteatosis.MethodsWith informed consent, 15 patients underwent nc-CT scan of the abdomen prior to weight loss surgery with intraoperative wedge and core needle liver biopsy. Mean left lobe nc-CT Hounsfield units (CTL), liver TG (mg/g Pr), HMS (%), BMI (kg/m2), liver-spleen index (CTL/S = hepatic HU/splenic HU), and liver–spleen difference (CTL-S = hepatic HU − splenic HU) were a priori outcomes.ResultsIn 15 patients (11 female) with a BMI of 44.4 ± 1.1 (mean ± SEM), CTL/S, CTL-S, and CTL measures were significantly associated with liver TG concentrations (r = −0.80, P < 0.001; r = −0.80, P < 0.001; and r = −0.71, P < 0.01, respectively; Table 1). Macrosteatosis (%) and liver triglyceride concentration were positively associated (r = 0.83; P < 0.0001). BMI did not correlate strongly to liver triglyceride (r = 0.44, P = NS).ConclusionEstimates of liver fat obtained by nc- CT scans (esp. CTL/S, CTL-S) correlate to chemical measurement of liver triglyceride concentrations, suggesting non-contrasted CT may be a suitable non-invasive “gold standard” for hepatic steatosis quantification in these patients.

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Models for Non-Alcoholic Fatty Liver Disease: A Link with Vascular Risk

Cited by 8 publications

References 71 publications

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet

Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet

Global Epidemiology of Nonalcoholic Fatty Liver Disease and Perspectives on US Minority Populations

Non-contrasted Computed Tomography for the Accurate Measurement of Liver Steatosis in Obese Patients

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