ArticleDiabetes2011
Apolipoprotein E4 exaggerates diabetic dyslipidemia and atherosclerosis in mice lacking the LDL receptor.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Egg consumption and cardiovascular risk: a dose-response meta-analysis of prospective cohort studies.European journal of nutrition · 2021Pooled it
- Apolipoprotein E Epsilon 4 Enhances the Association between the rs2910164 Polymorphism of miR-146a and Risk of Atherosclerotic Cerebral Infarction.Journal of atherosclerosis and thrombosis · 2016Trial
- APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses.Neurobiology of disease · 2025Article
- Egg consumption and risk of cardiovascular disease: a PERSIAN cohort-based study.BMC cardiovascular disorders · 2023Article
- Is type 2 diabetes associated dementia a microvascular early-Alzheimer's phenotype induced by aberrations in the peripheral metabolism of lipoprotein-amyloid?Frontiers in endocrinology · 2023Review
- The COVID-19 pandemic and Alzheimer's disease: mutual risks and mechanisms.Translational neurodegeneration · 2022Review
- Adiponectin overexpression in C2C12 myocytes increases lipid oxidation and myofiber transition.Journal of physiology and biochemistry · 2022Article
- ApoE and cerebral insulin: Trafficking, receptors, and resistance.Neurobiology of disease · 2020Review
- Apolipoprotein E4 mediates insulin resistance-associated cerebrovascular dysfunction and the post-prandial response.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy.Journal of lipid research · 2018Article
- γ-Secretase Inhibition Lowers Plasma Triglyceride-Rich Lipoproteins by Stabilizing the LDL Receptor.Cell metabolism · 2018Article
- Hyperglycemia Aggravates Diet-Induced Coronary Artery Disease and Myocardial Infarction in SR-B1-Knockout/ApoE-Hypomorphic Mice.Frontiers in physiology · 2018Article
- ApoE knockout and knockin mice: the history of their contribution to the understanding of atherogenesis.Journal of lipid research · 2016Article
- Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma.EBioMedicine · 2016Article
- Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.Journal of physiology and biochemistry · 2015Article
- Polymerase I and transcript release factor (PTRF) regulates adipocyte differentiation and determines adipose tissue expandability.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- A possible structural basis behind the pathogenic role of apolipoprotein E hereditary mutations associated with lipoprotein glomerulopathy.Clinical and experimental nephrology · 2014Review
- Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.Scientific reports · 2014Article
- Review
- Expression of human apolipoprotein E4 reduces insulin-receptor substrate 1 expression and Akt phosphorylation in the ageing liver.FEBS open bio · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe investigated the differential roles of apolipoprotein E (apoE) isoforms in modulating diabetic dyslipidemia-a potential cause of the increased cardiovascular disease risk of patients with diabetes. RESEARCH DESIGN AND
methodsDiabetes was induced using streptozotocin (STZ) in human apoE3 (E3) or human apoE4 (E4) mice deficient in the LDL receptor (LDLR(-/-)).
resultsDiabetic E3LDLR(-/-) and E4LDLR(-/-) mice have indistinguishable levels of plasma glucose and insulin. Despite this, diabetes increased VLDL triglycerides and LDL cholesterol in E4LDLR(-/-) mice twice as much as in E3LDLR(-/-) mice. Diabetic E4LDLR(-/-) mice had similar lipoprotein fractional catabolic rates compared with diabetic E3LDLR(-/-) mice but had larger hepatic fat stores and increased VLDL secretion. Diabetic E4LDLR(-/-) mice demonstrated a decreased reliance on lipid as an energy source based on indirect calorimetry. Lower phosphorylated acetyl-CoA carboxylase content and higher gene expression of fatty acid synthase in the liver indicated reduced fatty acid oxidation and increased fatty acid synthesis. E4LDLR(-/-) primary hepatocytes cultured in high glucose accumulated more intracellular lipid than E3LDLR(-/-) hepatocytes concomitant with a 60% reduction in fatty acid oxidation. Finally, the exaggerated dyslipidemia in diabetic E4LDLR(-/-) mice was accompanied by a dramatic increase in atherosclerosis.
conclusionsApoE4 causes severe dyslipidemia and atherosclerosis independent of its interaction with LDLR in a model of STZ-induced diabetes. ApoE4-expressing livers have reduced fatty acid oxidation, which contributes to the accumulation of tissue and plasma lipids.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.