کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5902984 1157043 2016 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease
ترجمه فارسی عنوان
مکانیسم های مولکولی سمیت لیپتوکسین و سمیت گلوتاتیک در بیماری کبدی چربی غیرالکلی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
چکیده انگلیسی

The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance in tissues. In this review, we highlight the lipids and carbohydrates that provoke hepatocyte injury and the mechanisms involved in lipotoxicity and glucotoxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment. Through upregulation of proteins involved in various pathways including PKR-like ER kinase (PERK), CCAAT/enhancer-binding homologous protein (CHOP), c-Jun NH2-terminal kinase-1 (JNK), Bcl-2 interacting mediator (BIM), p53 upregulated modulator of apoptosis (PUMA), and eventually caspases, hepatocytes in lipotoxic states ultimately undergo apoptosis. The protective role of certain lipids and possible targets for pharmacological therapy are explored. Finally, we discuss the role of high fructose and glucose diets in contributing to organelle impairment and poor glucose transport mechanisms, which perpetuate hyperglycemia and hyperlipidemia by shunting of excess carbohydrates into lipogenesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Metabolism - Volume 65, Issue 8, August 2016, Pages 1049-1061
نویسندگان
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