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A Potential Link Between Visceral Obesity and Risk of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is the most common type of dementia characterized by the deposition of amyloid beta (Aβ) plaques and tau-neurofibrillary tangles in the brain. Visceral obesity (VO) is usually associated with low-grade inflammation due to higher expression of pro-inflammatory cytokines by adipose tissue. The objective of the present review was to evaluate the potential link between VO and the development of AD. Tissue hypoxia in obesity promotes tissue injury, production of adipocytokines, and release of pro-inflammatory cytokines leading to an oxidative-inflammatory loop with induction of insulin resistance. Importantly, brain insulin signaling is involved in the pathogenesis of AD and lower cognitive function. Obesity and enlargement of visceral adipose tissue are associated with the deposition of Aβ. All of this is consonant with VO increasing the risk of AD through the dysregulation of adipocytokines which affect the development of AD. The activated nuclear factor kappa B (NF-κB) pathway in VO might be a potential link in the development of AD. Likewise, the higher concentration of advanced glycation end-products in VO could be implicated in the pathogenesis of AD. Taken together, different inflammatory signaling pathways are activated in VO that all have a negative impact on the cognitive function and progression of AD except hypoxia-inducible factor 1 which has beneficial and neuroprotective effects in mitigating the progression of AD. In addition, VO-mediated hypoadiponectinemia and leptin resistance may promote the progression of Aβ formation and tau phosphorylation with the development of AD. In conclusion, VO-induced AD is mainly mediated through the induction of oxidative stress, inflammatory changes, leptin resistance, and hypoadiponectinemia that collectively trigger Aβ formation and neuroinflammation. Thus, early recognition of VO by visceral adiposity index with appropriate management could be a preventive measure against the development of AD in patients with VO.

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Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Medicine, Medical Faculty, College of Medicine, Al-Mustansiriyah University, P.O. Box 14132, Baghdad, Iraq

    Hayder M. Al-Kuraishy & Ali I. Al-Gareeb

  2. Clinical Nutrition Department, Applied Medical Sciences College, Jazan University, Jazan, 82817, Saudi Arabia

    Abdulrahman A. Alsayegh

  3. Medical Laboratory Technology Department Applied Medical Sciences College, Jazan University, Jazan, 82817, Saudi Arabia

    Zaki H. Hakami

  4. Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia

    Nizar A. Khamjan

  5. Department of Pathology, Faculty of Veterinary Medicine, Matrouh University, Marsa Matruh, 51744, Egypt

    Hebatallah M. Saad

  6. Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt

    Gaber El-Saber Batiha

  7. Smartox Biotechnology, 6 rue des Platanes, 38120, Saint-Egrève, France

    Michel De Waard

  8. L’institut du thorax, INSERM, CNRS, UNIV NANTES, 44007, Nantes, France

    Michel De Waard

  9. LabEx «Ion Channels, Science & Therapeutics», Université de Nice Sophia-Antipolis, 06560, Valbonne, France

    Michel De Waard

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HMA, AIA, AAA and ZHH conceptualized the manuscript, wrote, edited and reviewed the main text and approved the final edition of the manuscript. NAK, HMS, GE-SB and MDW prepared the figures, wrote, corrected, amended and approved the final edition of the manuscript.

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Al-Kuraishy, H.M., Al-Gareeb, A.I., Alsayegh, A.A. et al. A Potential Link Between Visceral Obesity and Risk of Alzheimer’s Disease. Neurochem Res 48, 745–766 (2023). https://doi.org/10.1007/s11064-022-03817-4

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