Alzheimer’s disease (AD) remains a pressing public health concern, with its incidence increasing alongside aging populations and limited effective treatments[i]. Recent research by Dolatshahi et al. (2024) has shed light on a potential link between visceral fat and Alzheimer’s disease, hinting at a paradigm shift in understanding modifiable risk factors. This connection emphasises the importance of preventive strategies targeting metabolic health to mitigate Alzheimer’s risk. Having belly fat during your 40s and 50s may be a sign that the brain is already becoming sick and shrinking, increasing the risk of Alzheimer’s disease later in life.
Physiological Background
Visceral fat, a component of central obesity, plays a pivotal role in metabolic syndrome and insulin resistance[ii]. Excess visceral fat leads to chronic low-grade inflammation and oxidative stress, exacerbating systemic metabolic dysfunction[iii]. Chronic inflammation, characterised by elevated cytokines and adipokines, contributes to the accumulation of amyloid-β and tau proteins in the brain – hallmarks of Alzheimer’s pathology. Moreover, the gut-brain axis, a bidirectional communication network linking the central nervous system and the gastrointestinal tract, offers insight into how metabolic disturbances influence neurodegenerative processes[iv]. Disruptions in this axis may amplify neuroinflammation and neurodegeneration, rendering visceral fat a critical factor in Alzheimer’s disease development[v].
Visceral Fat and Alzheimer’s Disease: The Emerging Connection
Recent findings presented at the Radiological Society of North America (RSNA) provide compelling evidence linking visceral fat to Alzheimer’s disease. Results suggest that individuals with higher visceral fat levels exhibit abnormal brain protein deposits, detectable up to 20 years before clinical symptoms emerge. Potential mechanisms involve the secretion of adipokines and pro-inflammatory cytokines from visceral fat, crossing the blood-brain barrier and exacerbating neural inflammation[vi]. Additionally, visceral fat’s impact on insulin resistance and vascular health may impair glucose metabolism in the brain, a recognised contributor to Alzheimer’s pathology[vii].
Mechanisms Underlying Visceral Adipose Tissue-Mediated Neurotoxicity
Several mechanisms have been proposed to explain the neurotoxic effects of Visceral Adipose Tissue (VAT):
- Pro-inflammatory cytokines: VAT-secreted cytokines, such as IL-1β, TNF-α, and IL-6, stimulate neuroinflammation and oxidative stress, exacerbating AD pathology
- Free fatty acids: VAT-released FFAs induce insulin resistance, promoting Aβ production and neuronal apoptosis
- Lipotoxicity: Excess FFAs disrupt mitochondrial function, leading to energy deficits and neuronal degeneration
- Gut-brain axis: Alterations in gut microbiota composition, often seen in VAT dysregulation, modulate the brain-gut axis, influencing AD development
Implications for Prevention and Treatment
Early identification and modification of visceral fat are critical in reducing Alzheimer’s disease risk. Lifestyle interventions, including dietary modifications and regular physical activity, have proven effective in reducing visceral fat and improving metabolic health.
Nutritional strategies emphasising anti-inflammatory diets, such as the Mediterranean diet, may further mitigate risk. Exercise, particularly resistance training and aerobic activities, can also play a vital role in visceral fat reduction and cognitive health improvement. Emerging pharmacological and nutraceutical therapies targeting metabolic pathways offer additional tools for prevention. Agents such as GLP-1 receptor agonists and polyphenols are under investigation for their potential dual benefits in addressing visceral fat and cognitive decline[viii].
Conclusion
The association between visceral fat and Alzheimer’s disease underscores an urgent need for comprehensive strategies targeting modifiable risk factors. Proactive lifestyle interventions, combined with emerging therapeutic options, can help reduce Alzheimer’s disease’s burden on individuals and society. Further research is essential to translate these findings into actionable clinical practices and inform public health policies.
References
[i] Falsetti L. Molecular Research on Alzheimer’s Disease. Biomedicines. 2023 Jul 3;11(7):1883. doi: 10.3390/biomedicines11071883.
[ii] Diehl-Wiesenecker E, von Armin CA, Dupuis L, Müller HP, Ludolph AC, Kassubek J. Adipose Tissue Distribution in Patients with Alzheimer’s Disease: A Whole Body MRI Case-Control Study. J Alzheimers Dis. 2015;48(3):825-32.
[iii] Takase H, Dohi Y, Okado T, Hashimoto T, Goto Y, Kimura G. Effects of ezetimibe on visceral fat in the metabolic syndrome: a randomised controlled study. Eur J Clin Invest. 2012 Dec;42(12):1287-94. doi: 10.1111/eci.12000. Epub 2012 Oct 3. PMID: 23033884.
[iv] Cui QN, Stein LM, Fortin SM, Hayes MR. The role of glia in the physiology and pharmacology of glucagon-like peptide-1: implications for obesity, diabetes, neurodegeneration and glaucoma. Br J Pharmacol. 2022 Feb;179(4):715-726.
[v] Dandamudi BJ, Dimaano KAM, Shah N, AlQassab O, Al-Sulaitti Z, Nelakuditi B, Mohammed L. Neurodegenerative Disorders and the Gut-Microbiome-Brain Axis: A Literature Review. Cureus. 2024 Oct 26;16(10):e72427
[vi] Diehl-Wiesenecker E, von Armin CA, Dupuis L, Müller HP, Ludolph AC, Kassubek J. Adipose Tissue Distribution in Patients with Alzheimer’s Disease: A Whole Body MRI Case-Control Study. J Alzheimers Dis. 2015;48(3):825-32.
[vii] Ozato N, Saitou S, Yamaguchi T, Katashima M, Misawa M, Jung S, Mori K, Kawada H, Katsuragi Y, Mikami T, et al. Association between Visceral Fat and Brain Structural Changes or Cognitive Function. Brain Sciences. 2021; 11(8):1036.
[viii] Zelicha H, Kloting N, Kaplan A, Yaskolka Meir A, Rinott E, Tsaban G, Chassidim Y, Bluher M, Ceglarek U, Isermann B, Stumvoll M, Quayson RN, von Bergen M, Engelmann B, Rolle-Kampczyk UE, Haange SB, Tuohy KM, Diotallevi C, Shelef I, Hu FB, Stampfer MJ, Shai I. The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial. BMC Med. 2022 Sep 30;20(1):327.
