ArticlePloS one2015
Apolipoprotein D Transgenic Mice Develop Hepatic Steatosis through Activation of PPARγ and Fatty Acid Uptake.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review.Frontiers in physiology · 2021Pooled it
- Beneficial Changes in Apolipoprotein Concentrations After Bariatric Surgery in Obese Women.Metabolites · 2026Article
- Does glial lipid dysregulation alter sleep in Alzheimer's and Parkinson's disease?Trends in molecular medicine · 2024Review
- Apolipoprotein D in Oxidative Stress and Inflammation.Antioxidants (Basel, Switzerland) · 2023Review
- Apolipoprotein D modulates lipid mediators and osteopontin in an anti-inflammatory direction.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- A Short-Term High-Fat Diet Improved the Survival of Fat Grafts in Mice by Promoting Macrophage Infiltration and Angiogenesis.Frontiers in cell and developmental biology · 2022Article
- Adipose-Derived Lipid-Binding Proteins: The Good, the Bad and the Metabolic Diseases.International journal of molecular sciences · 2021Review
- Metabolic syndrome is a predictor of all site and liver-specific recurrence following primary resection of colorectal cancer: Prospective cohort study of 1006 patients.European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology · 2021Article
- Cerebral Apolipoprotein D Exits the Brain and Accumulates in Peripheral Tissues.International journal of molecular sciences · 2021Article
- Genome-wide transcriptome study using deep RNA sequencing for myocardial infarction and coronary artery calcification.BMC medical genomics · 2021Article
- The Role of cAMP-PKA Pathway in Lactate-Induced Intramuscular Triglyceride Accumulation and Mitochondria Content Increase in Mice.Frontiers in physiology · 2021Article
- Apolipoprotein D.Gene · 2020Review
- Plant-derived oleanolic acid ameliorates markers associated with non-alcoholic fatty liver disease in a diet-induced pre-diabetes rat model.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- High ApoD protein level in the round ligament fat depot of severely obese women is associated with an improved inflammatory profile.Endocrine · 2018Article
- Elevated HuR in Pancreas Promotes a Pancreatitis-Like Inflammatory Microenvironment That Facilitates Tumor Development.Molecular and cellular biology · 2018Article
- A molecular conundrum involving hypothalamic responses to and roles of long non-coding RNAs following food deprivation.Molecular and cellular endocrinology · 2016Review
- Reduced circulating levels of sTWEAK are associated with NAFLD and may affect hepatocyte triglyceride accumulation.International journal of obesity (2005) · 2016Observational
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration. Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance. We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice. Consequently, PPARγ target genes Plin2 and Cide A/C are overexpressed, leading to increased lipid droplets formation. Expression of the fatty acid transporter CD36, another PPARgamma target, is also increased in Tg mice associated with elevated fatty acid uptake as measured in primary hepatocytes. Elevated expression of AMPK in the liver of Tg leads to phosphorylation of acetyl CoA carboxylase, indicating a decreased activity of the enzyme. Fatty acid synthase expression is also induced but the hepatic lipogenesis measured in vivo is not significantly different between WT and Tg mice. In addition, expression of carnitine palmitoyl transferase 1, the rate-limiting enzyme of beta-oxidation, is slightly upregulated. Finally, we show that overexpressing H-apoD in HepG2 cells in presence of arachidonic acid (AA), the main apoD ligand, increases the transcriptional activity of PPARγ. Supporting the role of apoD in AA transport, we observed enrichment in hepatic AA and a decrease in plasmatic AA concentration. Taken together, our results demonstrate that the hepatic steatosis observed in apoD Tg mice is a consequence of increased PPARγ transcriptional activity by AA leading to increased fatty acid uptake by the liver.
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