Diagnosis and Therapy of Nonalcoholic Steatohepatitis

Torres, Dawn M.; Harrison, Stephen A.

doi:10.1053/j.gastro.2008.02.077

Cited by 319 publications

(299 citation statements)

References 159 publications

Supporting

Mentioning

253

Contrasting

Unclassified

Order By: Relevance

“…There is no single biochemical marker that can confirm a NAFLD diagnosis or distinguish between steatosis, NASH, and cirrhosis, but liver function tests abnormalities are common in patients with NAFLD, with elevations in ALT and AST usually no greater than four times the upper limit of normal (3,27,28). Liver biopsy is the gold standard for the diagnosis of NAFLD, considering that it is the only method that can distinguish between simple steatosis, NASH, and the degree of fibrosis (29,30).…”

Section: Discussionmentioning

confidence: 99%

Hypercholesterolemic diet induces hepatic steatosis and alterations in mRNA expression of NADPH oxidase in rat livers

Abreu

Guerra

Pereira

et al. 2014

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

Objective: This study aimed to determine whether a hypercholesterolemic diet induces hepatic steatosis, alterations in mRNA expression of NADPH oxidase subunits, and antioxidant defenses. Materials and methods: Fischer rats were divided into two groups of eight animals according to the treatment, control (C) and hypercholesterolemic diet (H). Those in group C were fed a standard diet (AIN-93M), and those of the group H were fed a hypercholesterolemic diet (25% soybean oil and 1% cholesterol). Results: The hypercholesterolemic diet did not affect body weight, but resulted in the accumulation of lipids in the liver, increased serum activities of aminotransferases and cholesterol levels. Biomarker of lipid peroxidation (TBARS) and mRNA expression of NADPH oxidase subunits p22 phox and p47 phox were increased in the liver of animals in group H. Besides, the activity and expression of antioxidant enzymes were altered. Conclusion:The results show increased mRNA expression of NADPH oxidase subunits and changes in antioxidant enzyme activities in diet-induced hepatic steatosis. Arq Bras Endocrinol Metab. 2014;58(3):251-9 Keywords Antioxidant enzymes; hepatic steatosis; hypercholesterolemic diet; NADPH oxidase; non-alcoholic fatty liver disease; oxidative stress RESUMO Objetivo: Determinar se uma dieta hipercolesterolemiante induz esteatose hepática, alterações na expressão de mRNA da NADPH oxidase e nas defesas antioxidantes. Materiais e métodos: Ratas Fischer foram divididas em dois grupos de oito animais de acordo com o tratamento recebido, controle (C) e hipercolesterolêmico (H). Aquelas do grupo C foram alimentadas com dieta padrão (AIN-93M) e as do grupo H foram alimentadas com dieta hipercolesterolemiante (25% de óleo de soja e 1% de colesterol). As dietas foram oferecidas por oito semanas. Resultados: O grupo H apresentou acúmulo de lipídios no fígado, aumento das atividades de ALT e AST e da concentração de colesterol no soro comparado ao grupo C. O marcador da peroxidação lipídica (TBARS) e os níveis de mRNA das subunidades p47 phox da NADPH-oxidase e p22 phox foram aumentados no fígado de animais do grupo H, além de alteração da atividade e expressão de enzimas antioxidantes. Conclusão: Os resultados mostram um aumento na expressão de subunidades da NADPH oxidase e alterações na atividade das enzimas antioxidantes na esteatose hepática induzida por dieta hipercolesterolemiante. Arq Bras Endocrinol Metab. 2014;58(3):251-9 Descritores Enzimas antioxidantes; esteatose hepática; dieta hipercolesterolemiante; NADPH oxidase; doença hepática gordurosa não alcoólica; estresse oxidativo

show abstract

Section: Discussionmentioning

confidence: 99%

Hypercholesterolemic diet induces hepatic steatosis and alterations in mRNA expression of NADPH oxidase in rat livers

Abreu

Guerra

Pereira

et al. 2014

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

show abstract

“…This is known as the first 'hit'. These changes make the liver more susceptible to a second 'hit', resulting in inflammation and the progression of liver damage [12]. Oxidative stress, mainly caused by mitochondrial dysfunction and pro-inflammatory cytokines, is believed to play an important role in the progression of liver damage in NAFLD.…”

Section: Non-alcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

“…Most cases of NAFLD are asymptomatic, and liver disease is often discovered incidentally when laboratory examination reveals elevated levels of liver enzymes [12]. In fact, elevated levels of liver enzymes alanine aminotransferase ( ALT) and/or aspartate aminotransferase ( AST) are commonly associated with NAFLD.…”

Section: Non-alcoholic Fatty Liver Disease (Nafld)mentioning

confidence: 99%

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

Duric

Sivanesan

Bakovic

2012

Euro J Lipid Sci & Tech

View full text Add to dashboard Cite

Non‐alcoholic fatty liver disease (NAFLD) is the most common liver condition in the developed world and may progress to more severe forms of disease such as cirrhosis or liver cancer. Thus, steps taken to reduce its prevalence through preventative nutritional approaches such as functional foods and nutraceuticals (FFN) should be pursued. It is well known that certain lipotropic nutrients such as choline and metabolites betaine and phosphatidylcholine (PC; lecithin) could prevent or alleviate fatty liver through a variety of mechanisms, including increased hepatic VLDL secretion. Animal and human studies have demonstrated clear protective effects of choline, betaine and PC for NAFLD as well as possible roles in CVD prevention from epidemiological data. Currently, choline consumption is below dietary recommendations due in large part to a general lack of understanding regarding the importance of this nutrient for human health. As lecithin is commonly added (in small amounts) in many processed foods due to its functional capabilities, it is projected that increasing its abundance in the food supply and increasing consumer education and acceptance of lecithin‐based functional foods and nutraceuticals may represent a progressive step towards preventing liver and whole‐body metabolic pathologies in many areas of the world.

show abstract

“…Nonalcoholic fatty liver disease (NAFLD) 4 is characterized by excessive lipid deposition in the liver of subjects with little alcohol consumption. Patients with NAFLD are at heightened risk of developing steatohepatitis with potential complications of fibrosis and cirrhosis (1)(2)(3)(4).…”

mentioning

confidence: 99%

“…Patients with NAFLD are at heightened risk of developing steatohepatitis with potential complications of fibrosis and cirrhosis (1)(2)(3)(4). Currently, NAFLD affects about 30% of the general population, and its prevalence is increasing along with the rising epidemic of obesity in both adults and children (1,(5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%

APOC3 Protein Is Not a Predisposing Factor for Fat-induced Nonalcoholic Fatty Liver Disease in Mice

Cheng

Yamauchi

Lee

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Jeffrey E. PessinNonalcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in liver, is prevalent in obesity. Genetic factors that link obesity to NAFLD remain obscure. Apolipoprotein C3 (APOC3) is a lipid-binding protein with a pivotal role in triglyceride metabolism. Humans with APOC3 gain-of-function mutations and mice with APOC3 overproduction are associated with hypertriglyceridemia. Nonetheless, it remains controversial whether APOC3 is culpable for diet-induced NAFLD. To address this fundamental issue, we fed APOC3-transgenic and wild-type littermates a high fructose diet or high fat diet, followed by determination of the effect of APOC3 on hepatic lipid metabolism and inflammation and the progression of NAFLD. To gain mechanistic insight into NAFLD, we determined the impact of APOC3 on hepatic triglyceride synthesis and secretion versus fatty acid oxidation. APOC3-transgenic mice were hypertriglyceridemic, culminating in marked elevation of triglycerides, cholesterols, and nonesterified fatty acids in plasma. Despite the prevailing hypertriglyceridemia, APOC3-transgenic mice, relative to wild-type littermates, had similar weight gain and hepatic lipid content without alterations in hepatic expression of key genes involved in triglyceride synthesis and secretion and fatty acid oxidation. APOC3-transgenic and wild-type mice had similar Kupffer cell content without alterations in hepatic expression of pro-and anti-inflammatory cytokines. APOC3 neither exacerbated dietinduced adiposity nor aggravated the degree of steatosis in high fructose or high fat-fed APOC3-transgenic mice. These effects ensued independently of weight gain even after 10-month high fat feeding. We concluded that APOC3, whose dysregulation is liable for hypertriglyceridemia, is not a predisposing factor for linking overnutrition to NAFLD in obesity. Nonalcoholic fatty liver disease (NAFLD)4 is characterized by excessive lipid deposition in the liver of subjects with little alcohol consumption. Patients with NAFLD are at heightened risk of developing steatohepatitis with potential complications of fibrosis and cirrhosis (1-4). Currently, NAFLD affects about 30% of the general population, and its prevalence is increasing along with the rising epidemic of obesity in both adults and children (1, 5-10). Although it is known that NAFLD results from increased lipogenesis and decreased fatty acid oxidation in the liver, accompanied often by hepatic overproduction of TG-rich very low density lipoprotein (VLDL-TG), genetic factors that tip the balance of these three intertwining pathways in hepatic lipid metabolism at the expense of NAFLD are incompletely characterized.Apolipoprotein C3 (APOC3) (79 amino acids in length) is one of the most abundant apolipoproteins in the blood, where it is present as an exchangeable moiety between high density lipoproteins (HDLs) and triglyceride (TG)-rich particles, such as VLDL and chylomicrons (11). Secreted mainly from the liver and to a lesser extent from the intestine, AP...

show abstract

Diagnosis and Therapy of Nonalcoholic Steatohepatitis

Cited by 319 publications

References 159 publications

Hypercholesterolemic diet induces hepatic steatosis and alterations in mRNA expression of NADPH oxidase in rat livers

Hypercholesterolemic diet induces hepatic steatosis and alterations in mRNA expression of NADPH oxidase in rat livers

Phosphatidylcholine functional foods and nutraceuticals: A potential approach to prevent non‐alcoholic fatty liver disease

APOC3 Protein Is Not a Predisposing Factor for Fat-induced Nonalcoholic Fatty Liver Disease in Mice

Contact Info

Product

Resources

About