Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition
| العنوان: | Insulin resistance dysregulates CYP7B1 leading to oxysterol accumulation: a pathway for NAFL to NASH transition |
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| المؤلفون: | Rebecca K. Martin, Mitsuyoshi Suzuki, Sandra A. LaSalle, Daniel Rodriguez-Agudo, Phillip B. Hylemon, Dalila Marques, Michael Fuchs, Hiroshi Nittono, Genta Kakiyama, Tsuyoshi Murai, William M. Pandak, Hajime Takei, Taishi Hashiguchi, Gregorio Gil, Huiping Zhou, Richard M. Green, Sandra K. Erickson, Xiaoying Liu |
| المصدر: | J Lipid Res Journal of Lipid Research, Vol 61, Iss 12, Pp 1629-1644 (2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | nonalcoholic fatty liver disease, 0301 basic medicine, Oxysterol, CYP7B1, Cytochrome P450 Family 7, QD415-436, 030204 cardiovascular system & hematology, Bioinformatics, Biochemistry, 03 medical and health sciences, Mice, 0302 clinical medicine, Endocrinology, Insulin resistance, Downregulation and upregulation, Non-alcoholic Fatty Liver Disease, Diabetes mellitus, Nonalcoholic fatty liver disease, medicine, Animals, Humans, nonalcoholic steatohepatitis, Research Articles, business.industry, Steroidogenic acute regulatory protein, Fatty liver, Cell Biology, Oxysterols, oxysterol 7α-hydroxylase, medicine.disease, digestive system diseases, 030104 developmental biology, Liver, inflammation, Steroid Hydroxylases, Hepatocytes, cholesterol toxicity, Insulin Resistance, business, liver injury |
| الوصف: | NAFLD is an important public health issue closely associated with the pervasive epidemics of diabetes and obesity. Yet, despite NAFLD being among the most common of chronic liver diseases, the biological factors responsible for its transition from benign nonalcoholic fatty liver (NAFL) to NASH remain unclear. This lack of knowledge leads to a decreased ability to find relevant animal models, predict disease progression, or develop clinical treatments. In the current study, we used multiple mouse models of NAFLD, human correlation data, and selective gene overexpression of steroidogenic acute regulatory protein (StarD1) in mice to elucidate a plausible mechanistic pathway for promoting the transition from NAFL to NASH. We show that oxysterol 7α-hydroxylase (CYP7B1) controls the levels of intracellular regulatory oxysterols generated by the “acidic/alternative” pathway of cholesterol metabolism. Specifically, we report data showing that an inability to upregulate CYP7B1, in the setting of insulin resistance, results in the accumulation of toxic intracellular cholesterol metabolites that promote inflammation and hepatocyte injury. This metabolic pathway, initiated and exacerbated by insulin resistance, offers insight into approaches for the treatment of NAFLD. |
| تدمد: | 1539-7262 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::104d469d4ac284995060021ac791a71d https://pubmed.ncbi.nlm.nih.gov/33008924 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....104d469d4ac284995060021ac791a71d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15397262 |
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