Influence of Exercise and Genistein to Mitigate the Deleterious Effects of High-Fat High-Sugar Diet on Alzheimer's Disease-Related Markers in Male Mice

The prevalence of obesity and related consequences, including insulin resistance and Alzheimer's-like neuropathology, has increased dramatically. Contributing to this prevalence is the shift in lifestyle preference away from wholesome foods and exercise to the Western-style diet and sedentarism...

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Published in:	International journal of molecular sciences Vol. 25; no. 16; p. 9019
Main Authors:	Shah, Juhi, Orosz, Tyler, Singh, Avneet, Laxma, Savan Parameshwar, Gross, Rachel E, Smith, Nicholas, Vroegop, Spencer, Sudler, Sydney, Porter, James T, Colon, Maria, Jun, Lauren, Babu, Jeganathan R, Shim, Minsub, Broderick, Thomas L, Al-Nakkash, Layla
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 20-08-2024 MDPI
Subjects:	Alzheimer Disease - etiology Alzheimer Disease - metabolism Alzheimer’s disease Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Amyloid Precursor Protein Secretases - metabolism Animals Apoptosis Biomarkers Body Weight - drug effects brain Brain - drug effects Brain - metabolism Brain - pathology Brain-derived neurotrophic factor Caspase 3 - metabolism Chronic illnesses Diabetes Diet Diet, High-Fat - adverse effects Dietary Sugars - adverse effects Disease Disease Models, Animal Exercise Fitness training programs Food genistein Genistein - pharmacology Genistein - therapeutic use high-fat diet Insulin Resistance Kinases Male Metabolism Mice Mice, Inbred C57BL Obesity Pathophysiology Physical Conditioning, Animal Physical fitness Proteins sucrose Tumor Necrosis Factor-alpha - metabolism exercise Alzheimer’s disease genistein brain sucrose high-fat diet
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Summary:	The prevalence of obesity and related consequences, including insulin resistance and Alzheimer's-like neuropathology, has increased dramatically. Contributing to this prevalence is the shift in lifestyle preference away from wholesome foods and exercise to the Western-style diet and sedentarism. Despite advances in drug development, a healthy diet and regular exercise remain the most effective approaches to mitigating the unwanted sequelae of diet-induced obesity on brain health. In this study, we used the high-fat high-sugar (HFHS) mouse model of neurodegeneration to examine the effects of exercise training (HFHS+Ex), genistein treatment (HFHS+Gen), and combination treatment (HFHS+Ex+Gen) on proteins relating to neurodegeneration in the brain of male mice. After a period of 12 weeks, as expected, HFHS feeding increased body weight, adipose tissue weight, and systemic plasma inflammation (TNF-α) compared to lean mice fed a standard diet. HFHS feeding also increased protein expression of brain markers of insulin resistance (pGSK-3β, p-IR), apoptosis (caspase 3), early neurofibrillary tangles (CP13), and amyloid-beta precursor (CT20). Compared to HFHS mice, Ex decreased body weight, plasma TNF-α, and expression of pGSK-3β, caspase 3, CP13, amyloid-β precursor (22c11), and ADAM10. Treatment with Gen was equally protective on these markers and decreased the expression of p-IR. Combination treatment with Ex and Gen afforded the greatest overall benefits, and this group exhibited the greatest reduction in body and adipose tissue weight and all brain markers, except for 22c11 and ADAM10, which were decreased compared to mice fed an HFHS diet. In addition, levels of 4G8, which detects protein levels of amyloid-β, were decreased with combination treatment. Our results indicate that exercise training, genistein supplementation, or combination treatment provide varying degrees of neuroprotection from HFHS feeding-induced Alzheimer's pathology. Future perspectives could include evaluating moderate exercise regimens in combination with dietary supplementation with genistein in humans to determine whether the same benefits translate clinically.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1661-6596 1422-0067 1422-0067
DOI:	10.3390/ijms25169019