Hepatic COX-2 expression protects mice from an alcohol-high fat diet-induced metabolic disorder by involving protein acetylation related energy metabolism
العنوان: | Hepatic COX-2 expression protects mice from an alcohol-high fat diet-induced metabolic disorder by involving protein acetylation related energy metabolism |
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المؤلفون: | Marta Casado, Liya Pi, Wei Wei, Minjie Chen, Xicui Sun, Qi Cao, Paloma Martín-Sanz, Carme Cucarella, Bin Ren |
المساهمون: | National Institutes of Health (US), Ministerio de Economía y Competitividad (España) |
المصدر: | Alcohol (Fayetteville, N.Y.) Digital.CSIC. Repositorio Institucional del CSIC instname |
سنة النشر: | 2021 |
مصطلحات موضوعية: | Male, medicine.medical_specialty, Health (social science), Liquid diet, White adipose tissue, Protein acetylation, Toxicology, Diet, High-Fat, Biochemistry, Article, 03 medical and health sciences, Behavioral Neuroscience, chemistry.chemical_compound, Mice, 0302 clinical medicine, Fatty liver disease, Internal medicine, medicine, Animals, Protein kinase B, Liver injury, Triglyceride, Chemistry, Cholesterol, Metabolic disorder, protein acetylation, Acetylation, General Medicine, COX-2, medicine.disease, Lipid Metabolism, 030227 psychiatry, Mice, Inbred C57BL, Endocrinology, Metabolism, Neurology, Liver, Cyclooxygenase 2, fatty liver disease, Steatosis, Energy Metabolism, metabolism, 030217 neurology & neurosurgery |
الوصف: | 12 páginas, 5 figuras, 2 tablas Purpose: A diet high in fat and ethanol often results in chronic metabolic disorder, hepatic steatosis, and liver inflammation. Constitutive hepatic cyclooxygenase-2 (COX-2) expression could protect from high fat-induced metabolism disturbance in a murine model. In this study, we explored the influence of hCOX-2 transgenic [TG] to high fat with ethanol-induced metabolic disorder and liver injury using a mouse animal model. Methods: 12-week-old male hepatic hCOX-2 transgenic (TG) or wild type mice (WT) were fed either a high fat and ethanol liquid diet (HF+Eth) or a regular control diet (RCD) for 5 weeks (four groups: RCD/WT, RCD/TG; HF+Eth/TG, HF+Eth/WT). We assessed metabolic biomarkers, cytokine profiles, histomorphology, and gene expression to study the impact of persistent hepatic COX-2 expression on diet-induced liver injury. Results: In the HF+Eth diet, constitutively hepatic human COX-2 expression protects mice from body weight gain and white adipose tissue accumulation, accompanied by improved IPGTT response, serum triglyceride/cholesterol levels, and lower levels of serum and liver inflammatory cytokines. Histologically, hCOX-2 mice showed decreased hepatic lipid droplets accumulation, decreased hepatocyte ballooning, and improved steatosis scores. Hepatic hCOX-2 overexpression enhanced AKT insulin signaling and increased fatty acid synthesis in both RCD and HF+Eth diet groups. The anti-lipogenic effect of hCOX-2 TG in the HF+Eth diet animals was mediated by increasing lipid disposal through enhanced β-oxidation via elevations in the expression of PPARα and PPARγ, and increased hepatic autophagy as assessed by the ratio of autophagy markers LC3 II/I in hepatic tissue. Various protein acetylation pathway components, including HAT, HDAC1, SIRT1, and SNAIL1, were modulated in hCOX-2 TG mice in either RCD or HF+Eth diet. Conclusions: Hepatic human COX-2 expression protected mice from the metabolic disorder and liver injury induced by a high fat and ethanol diet by enhancing hepatic lipid expenditure. Epigenetic reprogramming of diverse metabolic genes might be involved in the anti-lipogenic effect of COX-2. This work was supported by NIH grant (K08AA024895 to Q.C), Department Chair Research Fund of UMB (Q.C), GE Healthcare/ RSNA Research Resident Grant (#RR1250 to Q.C), Innovation Seed Grant of UMB (Q.C), Ministry of Economy and Competitiveness (MINECO, Spain. SAF2016-75004-R to P.M.S. and M.C) and NIH grant (1R01AA028035-01 to L.P). |
اللغة: | English |
تدمد: | 1873-6823 0741-8329 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89ddf36ac5ef4491264f586cb5c1bc7f http://europepmc.org/articles/PMC8095085 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....89ddf36ac5ef4491264f586cb5c1bc7f |
قاعدة البيانات: | OpenAIRE |
تدمد: | 18736823 07418329 |
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