ArticleAging cell2018
Ghrelin deletion protects against age-associated hepatic steatosis by downregulating the C/EBPα-p300/DGAT1 pathway.
Article in Aging cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Resveratrol Alleviates Arsenic-Induced Liver Fibrosis in Rats by Correcting SIRT1-Mediated Disorder of Hepatic Bile Acid Metabolism.International journal of molecular sciences · 2026Article
- Genetic Ablation of C/EBPα-p300 Pathway Blocks Development of Obese Pregnancy Associated Liver Disorders in Offspring.Cellular and molecular gastroenterology and hepatology · 2024Article
- Molecular and cellular mechanisms underlying the hepatoprotective role of ghrelin against NAFLD progression.Journal of physiology and biochemistry · 2023Review
- C/EBPα promotes triacylglycerol synthesis via regulating PPARG promoter activity in goat mammary epithelial cells.Journal of animal science · 2023Article
- Ghrelin regulating liver activity and its potential effects on liver fibrosis andFrontiers in cellular and infection microbiology · 2023Review
- Role of the Ghrelin System in Colitis and Hepatitis as Risk Factors for Inflammatory-Related Cancers.International journal of molecular sciences · 2022Review
- Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?Biology · 2022Review
- CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.Research (Washington, D.C.) · 2022Review
- Article
- Pluripotent Stem Cell-Derived Hepatocytes Phenotypic Screening Reveals Small Molecules Targeting the CDK2/4-C/EBPα/DGAT2 Pathway Preventing ER-Stress Induced Lipid Accumulation.International journal of molecular sciences · 2020Article
- Valproic acid promotes mitochondrial dysfunction in primary human hepatocytes in vitro; impact of C/EBPα-controlled gene expression.Archives of toxicology · 2020Article
- Aging-induced aberrant RAGE/PPARα axis promotes hepatic steatosis via dysfunctional mitochondrial β oxidation.Aging cell · 2020Article
- Recent progress in the discovery of ghrelinRSC medicinal chemistry · 2020Review
- Ghrelin and liver disease.Reviews in endocrine & metabolic disorders · 2020Review
- DOCK5 regulates energy balance and hepatic insulin sensitivity by targeting mTORC1 signaling.EMBO reports · 2020Article
- Liver Proliferation Is an Essential Driver of Fibrosis in Mouse Models of Nonalcoholic Fatty Liver Disease.Hepatology communications · 2019Article
- Immune-Deficient Pfp/Rag2Cells · 2019Article
- Wheat Flour, Enriched with γ-Oryzanol, Phytosterol, and Ferulic Acid, Alleviates Lipid and Glucose Metabolism in High-Fat-Fructose-Fed Rats.Nutrients · 2019Article
- Correction of aging phenotype in the liver.Aging · 2018Article
- Elimination of Age-Associated Hepatic Steatosis and Correction of Aging Phenotype by Inhibition of cdk4-C/EBPα-p300 Axis.Cell reports · 2018Article
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7 authors at 2 institutions in 2 countries.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. NAFLD usually begins as low-grade hepatic steatosis which further progresses in an age-dependent manner to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma in some patients. Ghrelin is a hormone known to promote adiposity in rodents and humans, but its potential role in hepatic steatosis is unknown. We hypothesized that genetic ghrelin deletion will protect against the development of age-related hepatic steatosis. To examine this hypothesis, we utilized ghrelin knockout (KO) mice. Although no different in young animals (3 months old), we found that at 20 months of age, ghrelin KO mice have significantly reduced hepatic steatosis compared to aged-matched wild-type (WT) mice. Examination of molecular pathways by which deletion of ghrelin reduces steatosis showed that the increase in expression of diacylglycerol O-acyltransferase-1 (DGAT1), one of the key enzymes of triglyceride (TG) synthesis, seen with age in WT mice, is not present in KO mice. This was due to the lack of activation of CCAAT/enhancer binding protein-alpha (C/EBPα) protein and subsequent reduction of C/EBPα-p300 complexes. These complexes were abundant in livers of old WT mice and were bound to and activated the DGAT1 promoter. However, the C/EBPα-p300 complexes were not detected on the DGAT1 promoter in livers of old KO mice resulting in lower levels of the enzyme. In conclusion, these studies demonstrate the mechanism by which ghrelin deletion prevents age-associated hepatic steatosis and suggest that targeting this pathway may offer therapeutic benefit for NAFLD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.