Journal
NEUROBIOLOGY OF DISEASE
Volume 138, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2020.104809
Keywords
Mechanisms; Obesity; Review; Diabetes; Fertility
Categories
Funding
- Institute de Salud Carlos III [PI17/02268]
- Fondo Europeo de Desarrollo Regional (FEDER): Una manera de hacer Europa
- Miguel Servet fellowship (Institute de Salud Carlos III)
- DGA Group Biology of adipose tissue and metabolic complications [1303_17R]
- FEDER Aragon 2014-2020: Construyendo Europa desde Aragon
- National Institute of General Medical [T32GM118292-03]
- National Institute on Aging [1R01AG060056-01, R01AG060056 02]
- National Institute of General Medical Sciences [COBRE P20 GM103527]
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Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (epsilon 2, epsilon 3, and epsilon 4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with demonstrated roles across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.
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