ArticleInternational journal of obesity (2005)2016
Metabolic shifts toward fatty-acid usage and increased thermogenesis are associated with impaired adipogenesis in mice expressing human APOE4.
Article in International journal of obesity (2005), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 49 citations in OpenAlex.
- Review
- Article
- Targeting the astrocytic metabolic cascade in Alzheimer's disease: mechanisms, challenges and opportunities.Frontiers in aging neuroscience · 2026Review
- Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype.Journal of neuroinflammation · 2025Article
- Circulating non-esterified fatty acids, risk of dementia and cognitive decline: The cardiovascular health study and multi-ethnic study of atherosclerosis.Neurobiology of aging · 2025Article
- Lipid Oxidation at the Crossroads: Oxidative Stress and Neurodegeneration Explored inAntioxidants (Basel, Switzerland) · 2025Review
- Effects of West Nile virus on behavioral and cognitive performance, cortical Aβ pathology, viral loads, and immune measures of middle-aged NL-G-F/E3 and NL-G-F/E4 mice.Frontiers in aging neuroscience · 2025Article
- The Brain-Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review.Journal of clinical medicine · 2024Review
- Obesity affects brain cortex gene expression in an APOE genotype and sex dependent manner.International journal of obesity (2005) · 2024Article
- Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3.Aging and disease · 2024Article
- Effects of obesogenic diet and 17β-estradiol in female mice withFrontiers in aging neuroscience · 2024Article
- The novel estrogen receptor beta agonist EGX358 andFrontiers in aging neuroscience · 2024Article
- Ketone body metabolism and cardiometabolic implications for cognitive health.npj metabolic health and disease · 2024Article
- Predictive link between systemic metabolism and cytokine signatures in the brain of apolipoprotein E ε4 mice.Neurobiology of aging · 2023Article
- Effects ofMetabolites · 2023Article
- Exercise modulates APOE expression in brain cortex of female APOE3 and APOE4 targeted replacement mice.Neuropeptides · 2023Article
- Relationship of Muscle Apolipoprotein E Expression with Markers of Cellular Stress, Metabolism, and Blood Biomarkers in Cognitively Healthy and Impaired Older Adults.Journal of Alzheimer's disease : JAD · 2023Article
- Apolipoprotein E in Cardiometabolic and Neurological Health and Diseases.International journal of molecular sciences · 2022Review
- Association betweenInternational journal of molecular sciences · 2022Article
- Apolipoprotein E and Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundThe Apolipoprotein E (APOE) gene encodes for three isoforms in the human population (APOE2, APOE3 and APOE4). Whereas the role of APOE in lipid metabolism is well characterized, the specific metabolic signatures of the APOE isoforms during metabolic disorders, remain unclear.
objectiveTo elucidate the molecular underpinnings of APOE-directed metabolic alterations, we tested the hypothesis that APOE4 drives a whole-body metabolic shift toward increased lipid oxidation.
methodsWe employed humanized mice in which the Apoe gene has been replaced by the human APOE*3 or APOE*4 allele to produce human APOE3 or APOE4 proteins and characterized several mechanisms of fatty-acid oxidation, lipid storage, substrate utilization and thermogenesis in those mice.
resultsWe show that, whereas APOE4 mice gained less body weight and mass than their APOE3 counterparts on a Western-type diet (P<0.001), they displayed elevated insulin and homeostatic model assessment, markers of insulin resistance (P=0.004 and P=0.025, respectively). APOE4 mice also demonstrated a reduced respiratory quotient during the postprandial period (0.95±0.03 versus 1.06±0.03, P<0.001), indicating increased usage of lipids as opposed to carbohydrates as a fuel source. Finally, APOE4 mice showed increased body temperature (37.30±0.68 versus 36.9±0.58 °C, P=0.039), augmented cold tolerance and more metabolically active brown adipose tissue compared with APOE3 mice.
conclusionThese data suggest that APOE4 mice may resist weight gain via an APOE4-directed global metabolic shift toward lipid oxidation and enhanced thermogenesis, and may represent a critical first step in the development of APOE-directed therapies for a large percentage of the population affected by disorders with established links to APOE and metabolism.
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