Obesity as a Risk Factor for Dementia and Alzheimer’s Disease: The Role of Leptin
Open accessAbstract
Obesity is a growing worldwide health problem, affecting many people due to excessive saturated fat consumption, lack of exercise, or a sedentary lifestyle. Leptin is an adipokine secreted by adipose tissue that increases in obesity and has central actions not only at the hypothalamic level but also in other regions and nuclei of the central nervous system (CNS) such as the cerebral cortex and hippocampus. These regions express the long form of leptin receptor LepRb, which is the unique leptin receptor capable of transmitting complete leptin signaling, and are the first regions to be affected by chronic neurocognitive deficits, such as mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). In this review, we discuss different leptin resistance mechanisms that could be implicated in increasing the risk of developing AD, as leptin resistance is frequently associated with obesity, which is a chronic low-grade inflammatory state, and obesity is considered a risk factor for AD. Key players of leptin resistance are SOCS3, PTP1B, and TCPTP whose signalling is related to inflammation and could be worsened in AD. However, some data are controversial, and it is necessary to further investigate the underlying mechanisms of the AD-causing pathological processes and how altered leptin signalling affects such processes.
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The APOE ε4 allele greatly increases AD risk.
“The AD risk is greatly increased by the APOE ε4 allele.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [44]
A person with one copy of the APOE ε4 allele is more likely to be affected than a person with two copies.
“A person with one copy of this allele is more likely to be affected than a person with two copies [42,43,44].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [44]
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- [44]Fietta and Delsante Focus on Adipokines—PubMed Available online: https://pubmed.ncbi.nlm.nih.gov/24640423/ (accessed on 27 April 2022)
- [45]Effect of Body Mass Index on Serum Leptin Levels—PubMed Available online: https://pubmed.ncbi.nlm.nih.gov/23272432/ (accessed on 27 April 2022)
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- Authors
- Flores-Cordero, J. A., Pérez-Pérez, A., Jiménez-Cortegana, C., Alba, G., Flores-Barragán, A., & Sánchez-Margalet, V.
- Affiliations
- Hospital Universitario Virgen Macarena (ES)
- Department of Medical Biochemistry and Molecular Biology and Immunology, Medical School, Virgen Macarena University Hospital, University of Seville, Av. Sánchez Pizjuan 4, 41009 Sevilla, Spain
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2022-05-06
- Volume
- 23
- Issue
- 9
- Pages
- 5202
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC9099768
- OpenAlex
- W4229030955
- Cited by
- 212
- References
- 156
- Citations by year
- 2026: 30 · 2025: 64 · 2024: 64 · 2023: 45 · 2022: 9
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deposito de Investigacion Universidad de Sevilla (University of Seville) (submittedVersion, cc-by)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- Funders
- PAIDI CTS-151 Junta de Andalucia, Spain
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- obesity, Alzheimer's disease, dementia, leptin, leptin resistance, adipokines, SOCS3, PTP1B, TCPTP, neuroinflammation, mild cognitive impairment, hippocampus, cerebral cortex, hypothalamus, low-grade inflammation
- MeSH terms
- Alzheimer Disease, Humans, Obesity, Risk Factors, Leptin, Receptors, Leptin
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