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Apolipoprotein E in diet-induced obesity: a paradigm shift from conventional perception
Kyriakos E Kypreos1, Eleni A Karavia1, Caterina Constantinou1
1Department of Pharmacology, University of Patras Medical School, Rio Achaias, TK 26500, Greece.
Journal of Biomedical Research
|May 18, 2018
Summary
Apolipoprotein E3 (APOE3) in the brain inhibits fat oxidation, promoting obesity. However, liver APOE3 promotes fat burning, preventing obesity, challenging prior understanding of APOE and weight gain.
Area of Science:
- Metabolism and Endocrinology
- Neuroscience
- Cardiovascular Disease Research
Background:
- Apolipoprotein E (APOE) is crucial for lipid transport in both the periphery and brain.
- Peripheral and brain APOE systems are distinct, with minimal exchange across barriers.
- Epidemiological studies link peripheral APOE to heart disease and brain APOE to dementia/Alzheimer's.
Purpose of the Study:
- To critically review recent findings on the role of Apolipoprotein E in morbid obesity.
- To explore the novel paradigm shift in understanding APOE's influence on obesity.
- To differentiate the effects of brain versus hepatic APOE expression on adipose tissue metabolism.
Main Methods:
- Review of experimental mouse studies investigating APOE isoform effects on adipose tissue.
- Analysis of mitochondrial oxidative phosphorylation in visceral white adipose tissue (WAT).
- Assessment of substrate oxidation and fat accumulation in response to different APOE expression patterns.
Main Results:
- Brain-expressed Apolipoprotein E3 (APOE3) inhibits WAT mitochondrial oxidative phosphorylation, reducing substrate oxidation and causing obesity.
- Hepatically expressed APOE3 shifts substrate oxidation to thermogenesis in WAT mitochondria, conferring obesity resistance.
- These findings contrast with the established view of APOE promoting obesity via lipid delivery.
Conclusions:
- Brain APOE3 actively promotes obesity by impairing mitochondrial function in visceral fat.
- Liver APOE3 confers resistance to obesity by enhancing thermogenesis.
- The role of APOE in obesity is complex and isoform/location-dependent, necessitating a re-evaluation of previous models.
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