High-dose vitamin B1 therapy prevents the development of experimental fatty liver driven by overnutrition
| العنوان: | High-dose vitamin B1 therapy prevents the development of experimental fatty liver driven by overnutrition |
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| المؤلفون: | Uzi Moallem, Mugagga Kalyesubula, Hay Dvir, Jimmy Asiku, Samuel Bocobza, Ramgopal Mopuri, Alexander Rosov, Nir Edery, Sara Yosefi |
| المصدر: | Disease Models & Mechanisms, Vol 14, Iss 3 (2021) Disease Models & Mechanisms article-version (VoR) Version of Record |
| بيانات النشر: | The Company of Biologists, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Blood Glucose, Male, 0301 basic medicine, obesity, Medicine (miscellaneous), nafld, Weight Gain, Chronic liver disease, Overnutrition, 0302 clinical medicine, Immunology and Microbiology (miscellaneous), insulin resistance, Hyperinsulinemia, steatosis, Pathology, RB1-214, Adiposity, Fatty Acids, Fatty liver, food and beverages, Mitochondria, Liver, Cytokines, Medicine, 030211 gastroenterology & hepatology, Thiamine, Inflammation Mediators, Glycogen, Research Article, medicine.medical_specialty, Neuroscience (miscellaneous), Diet, High-Fat, General Biochemistry, Genetics and Molecular Biology, metabolic syndrome, thiamine, 03 medical and health sciences, Insulin resistance, Internal medicine, medicine, Animals, Ketoglutarate Dehydrogenase Complex, RNA, Messenger, fatty liver, Sheep, Dose-Response Relationship, Drug, business.industry, Lipid Metabolism, medicine.disease, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Thiamine Pyrophosphate, Steatosis, Metabolic syndrome, business |
| الوصف: | Fatty liver is an abnormal metabolic condition of excess intrahepatic fat. This condition, referred to as hepatic steatosis, is tightly associated with chronic liver disease and systemic metabolic morbidity. The most prevalent form in humans, i.e. non-alcoholic fatty liver, generally develops due to overnutrition and sedentary lifestyle, and has as yet no approved drug therapy. Previously, we have developed a relevant large-animal model in which overnourished sheep raised on a high-calorie carbohydrate-rich diet develop hyperglycemia, hyperinsulinemia, insulin resistance, and hepatic steatosis. Here, we tested the hypothesis that treatment with thiamine (vitamin B1) can counter the development of hepatic steatosis driven by overnutrition. Remarkably, the thiamine-treated animals presented with completely normal levels of intrahepatic fat, despite consuming the same amount of liver-fattening diet. Thiamine treatment also decreased hyperglycemia and increased the glycogen content of the liver, but it did not improve insulin sensitivity, suggesting that steatosis can be addressed independently of targeting insulin resistance. Thiamine increased the catalytic capacity for hepatic oxidation of carbohydrates and fatty acids. However, at gene-expression levels, more-pronounced effects were observed on lipid-droplet formation and lipidation of very-low-density lipoprotein, suggesting that thiamine affects lipid metabolism not only through its known classic coenzyme roles. This discovery of the potent anti-steatotic effect of thiamine may prove clinically useful in managing fatty liver-related disorders. This article has an associated First Person interview with the joint first authors of the paper. Editor's choice: Experiments using overnourished sheep raised on a high-calorie liver-fattening diet, treated with and without thiamine, revealed that vitamin B1 protects against the development of fatty liver driven by overnutrition. |
| اللغة: | English |
| تدمد: | 1754-8411 1754-8403 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa6e9664631ce2256dd948bb054bfce4 http://dmm.biologists.org/content/14/3/dmm048355 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fa6e9664631ce2256dd948bb054bfce4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17548411 17548403 |
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