{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:41:18Z","timestamp":1792860078575,"version":"4.5.0"},"reference-count":177,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The increasing prevalence of obesity and Alzheimer\u2019s disease (AD) in the aging population underscores an urgent need to understand the common cellular and metabolic mechanisms they share. Accumulated evidence suggests that overlapping metabolic disturbances contribute to the pathogenesis of these two conditions. In this review, we highlight key underlying interconnecting metabolic pathways: (1) adipose-brain crosstalk mediated by adipokines and adipose tissue-derived extracellular vesicles that can modulate neuronal function and amyloid pathology, (2) dysregulated lipid metabolism affecting cholesterol, sphingolipids, and phospholipids and thereby promoting inflammation, amyloid precursor protein processing, and tau hyperphosphorylation, (3) impaired glycolysis and insulin resistance, which accelerate both obesity and neurodegenerative processes, (4) mitochondrial dysfunction marked by disrupted tricarboxylic acid cycle enzymes and electron transport chain complexes, leading to elevated reactive oxygen species and driving both obesity and AD pathology, and (5) gut microbiota dysbiosis, which can trigger inflammation as well as amyloid and tau aggregation. Together, these mechanisms show that metabolic alterations appear early, preceding clinical disease, and that understanding these underlying connections can provide strategies to protect metabolic health and prevent disease progression.<\/jats:p>","DOI":"10.3390\/cells15080672","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:20:16Z","timestamp":1775816416000},"page":"672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["From Lipids to Mitochondria: Shared Metabolic Alterations in Obesity and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"given":"Romina Mar\u00eda","family":"Uranga","sequence":"first","affiliation":[{"name":"Natural Sciences Division, New College of Florida, 5800 Bay Shore Road, Sarasota, FL 34243, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailaja Kesaraju","family":"Allani","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, FL 33431, USA"},{"name":"Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science, Florida, Atlantic University, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","unstructured":"U.S. Census Bureau (2026, February 11). Older Population and Aging, Available online: https:\/\/www.census.gov\/library\/visualizations\/2025\/comm\/older-adults-comparable-to-children.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1002\/puh2.213","article-title":"Public Health Challenges and Responses to the Growing Ageing Populations","volume":"3","author":"Khan","year":"2024","journal-title":"Public Health Chall."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"(2024). Alzheimer\u2019s & Dementia. Alzheimer\u2019s Disease Facts and Figures. Alzheimer\u2019s Dement., 20, 3708\u20133821.","DOI":"10.1002\/alz.13809"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Choi, W., Woo, G.H., Kwon, T.-H., and Jeon, J.-H. (2025). Obesity-Driven Metabolic Disorders: The Interplay of Inflammation and Mitochondrial Dysfunction. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199715"},{"key":"ref_5","first-page":"1052","article-title":"Correlation between Obesity and Alzheimer\u2019s Disease and the Mechanisms","volume":"49","author":"Zhang","year":"2024","journal-title":"Zhong Nan Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/oxfordjournals.aje.a009680","article-title":"Voluntary and Involuntary Weight Loss: Associations with Long Term Mortality in 9228 Middle-Aged and Elderly Men","volume":"148","author":"Yaari","year":"1998","journal-title":"Am. J. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.annepidem.2004.12.003","article-title":"Associations with Weight Loss and Subsequent Mortality Risk","volume":"15","author":"Knudtson","year":"2005","journal-title":"Ann. Epidemiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.3945\/ajcn.110.006379","article-title":"The Effect of Intentional Weight Loss on All-Cause Mortality in Older Adults: Results of a Randomized Controlled Weight-Loss Trial","volume":"94","author":"Shea","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.jalz.2017.06.2637","article-title":"Obesity Trajectories and Risk of Dementia: 28 Years of Follow-up in the Whitehall II Study","volume":"14","author":"Dugravot","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1001\/archinte.168.15.1609","article-title":"Identification and Characterization of Metabolically Benign Obesity in Humans","volume":"168","author":"Stefan","year":"2008","journal-title":"Arch. Intern. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1210\/jc.2005-0482","article-title":"The Metabolically Healthy but Obese Individual Presents a Favorable Inflammation Profile","volume":"90","author":"Karelis","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI78425","article-title":"Metabolically Normal Obese People Are Protected from Adverse Effects Following Weight Gain","volume":"125","author":"Fabbrini","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1161\/CIRCULATIONAHA.109.887521","article-title":"Impact of Body Mass Index and the Metabolic Syndrome on the Risk of Cardiovascular Disease and Death in Middle-Aged Men","volume":"121","author":"Ingelsson","year":"2010","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1186\/s12967-025-06440-3","article-title":"Neuroinflammation and Energy Metabolism: A Dual Perspective on Ischemic Stroke","volume":"23","author":"Lei","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12979-024-00422-7","article-title":"Correction: Obesity-Induced Neuroinflammation and Cognitive Impairment in Young Adult versus Middle-Aged Mice","volume":"21","author":"Henn","year":"2024","journal-title":"Immun. Ageing"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Clemente-Su\u00e1rez, V.J., Redondo-Fl\u00f3rez, L., Beltr\u00e1n-Velasco, A.I., Mart\u00edn-Rodr\u00edguez, A., Mart\u00ednez-Guardado, I., Navarro-Jim\u00e9nez, E., Laborde-C\u00e1rdenas, C.C., and Tornero-Aguilera, J.F. (2023). The Role of Adipokines in Health and Disease. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051290"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1042\/CS20200895","article-title":"The Complex Role of Adipokines in Obesity, Inflammation, and Autoimmunity","volume":"135","author":"Taylor","year":"2021","journal-title":"Clin. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Uranga, R.M., and Keller, J.N. (2019). The Complex Interactions Between Obesity, Metabolism and the Brain. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00513"},{"key":"ref_19","first-page":"145","article-title":"Adipokines in Obesity and Metabolic Diseases","volume":"93","author":"Giammanco","year":"2021","journal-title":"Boll. Soc. Ital. Biol. Sper."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pedro, W.J.S., Barbosa J\u00fanior, F.V., Alves, F.N.B.R., Braga, L.V., Alves, L.R., Afonso, J.P.R., Silva, I.O., Silva, C.H.M., Vencio, S., and Capodaglio, P. (2025). Role of Adipokines Chemerin, Visfatin, and Omentin in Obesity and Their Inflammatory and Metabolic Implications. Biomedicines, 13.","DOI":"10.3390\/biomedicines13102321"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Kirichenko, T.V., Markina, Y.V., Bogatyreva, A.I., Tolstik, T.V., Varaeva, Y.R., and Starodubova, A.V. (2022). The Role of Adipokines in Inflammatory Mechanisms of Obesity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314982"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.jagp.2023.06.001","article-title":"Neuroinflammation: A Modifiable Pathway Linking Obesity, Alzheimer\u2019s Disease, and Depression","volume":"31","author":"Ly","year":"2023","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/27376","article-title":"Leptin and the Regulation of Body Weight in Mammals","volume":"395","author":"Friedman","year":"1998","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E1338","DOI":"10.1152\/ajpendo.00021.2013","article-title":"Leptin-Sensitive Sensory Nerves Innervate White Fat","volume":"304","author":"Murphy","year":"2013","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_25","first-page":"13","article-title":"The LepR-Mediated Leptin Transport across Brain Barriers Controls Food Reward","volume":"8","author":"Sandin","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s41366-018-0221-z","article-title":"Fluorescent Blood\u2013Brain Barrier Tracing Shows Intact Leptin Transport in Obese Mice","volume":"43","author":"Harrison","year":"2018","journal-title":"Int. J. Obes."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lee, T.H.Y., Cheng, K.K.Y., Hoo, R.L.C., Siu, P.M.F., and Yau, S.Y. (2019). The Novel Perspectives of Adipokines on Brain Health. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225638"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1016\/j.euroneuro.2014.03.002","article-title":"Obesity and Dementia: Adipokines Interact with the Brain","volume":"24","author":"Arnoldussen","year":"2014","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1159\/000108635","article-title":"Adipokine Gene Expression in Brain and Pituitary Gland","volume":"86","author":"Wilkinson","year":"2007","journal-title":"Neuroendocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.neulet.2007.12.008","article-title":"Traumatic Brain Injury Induces Adipokine Gene Expression in Rat Brain","volume":"432","author":"Brown","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_31","first-page":"2270","article-title":"Leptin Is Released from the Human Brain: Influence of Adiposity and Gender","volume":"84","author":"Wiesner","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.2337\/diabetes.55.01.06.db05-1077","article-title":"Adiponectin Does Not Cross the Blood-Brain Barrier but Modifies Cytokine Expression of Brain Endothelial Cells","volume":"55","author":"Spranger","year":"2006","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s00125-006-0577-9","article-title":"Adiponectin Complexes in Human Cerebrospinal Fluid: Distinct Complex Distribution from Serum","volume":"50","author":"Kusminski","year":"2007","journal-title":"Diabetologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1152\/ajpendo.00119.2007","article-title":"Detection of Adiponectin in Cerebrospinal Fluid in Humans","volume":"293","author":"Neumeier","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4593530","DOI":"10.1155\/2018\/4593530","article-title":"Role of Adiponectin in Central Nervous System Disorders","volume":"2018","author":"Bloemer","year":"2018","journal-title":"Neural Plast."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101397","DOI":"10.1016\/j.arr.2021.101397","article-title":"Western Diet as a Trigger of Alzheimer\u2019s Disease: From Metabolic Syndrome and Systemic Inflammation to Neuroinflammation and Neurodegeneration","volume":"70","author":"Wydrych","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.bbadis.2012.12.009","article-title":"Leptin Regulates Amyloid \u03b2 Production via the \u03b3-Secretase Complex","volume":"1832","author":"Niedowicz","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/jnc.12828","article-title":"Leptin Inhibits Amyloid \u03b2-Protein Fibrillogenesis by Decreasing GM1 Gangliosides on the Neuronal Cell Surface through PI3K\/Akt\/MTOR Pathway","volume":"131","author":"Yamamoto","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.peptides.2005.10.006","article-title":"Effects of Leptin on Memory Processing","volume":"27","author":"Farr","year":"2006","journal-title":"Peptides"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18238","DOI":"10.1074\/jbc.M800053200","article-title":"Leptin Increases Adult Hippocampal Neurogenesis in Vivo and in Vitro","volume":"283","author":"Garza","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15810","DOI":"10.1073\/pnas.1415219111","article-title":"Physical Exercise-Induced Hippocampal Neurogenesis and Antidepressant Effects Are Mediated by the Adipocyte Hormone Adiponectin","volume":"111","author":"Yaua","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s11064-017-2426-2","article-title":"Adiponectin Attenuates Streptozotocin-Induced Tau Hyperphosphorylation and Cognitive Deficits by Rescuing PI3K\/Akt\/GSK-3\u03b2 Pathway","volume":"43","author":"Xu","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100166","DOI":"10.1016\/j.jnha.2024.100166","article-title":"The Role of Adiponectin in Alzheimer\u2019s Disease: A Translational Review","volume":"28","author":"Sindzingre","year":"2024","journal-title":"J. Nutr. Health Aging"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3233\/JAD-180669","article-title":"Association between Adipokines and Biomarkers of Alzheimer\u2019s Disease: A Cross-Sectional Study","volume":"67","author":"Letra","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1186\/s13195-022-01107-3","article-title":"Plasma Adiponectin Levels Predict Cognitive Decline and Cortical Thinning in Mild Cognitive Impairment with Beta-Amyloid Pathology","volume":"14","author":"Kim","year":"2022","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/acn3.436","article-title":"Importance of Adiponectin Activity in the Pathogenesis of Alzheimer\u2019s Disease","volume":"4","author":"Waragai","year":"2017","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1759091415605114","DOI":"10.1177\/1759091415605114","article-title":"Intranasal Delivery of Apelin-13 Is Neuroprotective and Promotes Angiogenesis After Ischemic Stroke in Mice","volume":"7","author":"Chen","year":"2015","journal-title":"ASN Neuro"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s12031-014-0486-1","article-title":"Nampt\/PBEF\/Visfatin Exerts Neuroprotective Effects against Ischemia\/Reperfusion Injury via Modulation of Bax\/Bcl-2 Ratio and Prevention of Caspase-3 Activation","volume":"56","author":"Erfani","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Luo, H., Xiang, Y., Qu, X., Liu, H., Liu, C., Li, G., Han, L., and Qin, X. (2019). Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer\u2019s Disease Through Activation of BDNF-TrkB Signaling Pathway. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00395"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102554","DOI":"10.1016\/j.redox.2022.102554","article-title":"ChemR23 Signaling Ameliorates Cognitive Impairments in Diabetic Mice via Dampening Oxidative Stress and NLRP3 Inflammasome Activation","volume":"58","author":"Zhang","year":"2022","journal-title":"Redox Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"118702","DOI":"10.1016\/j.biopha.2025.118702","article-title":"Chemerin-CMKLR1 Differentially Mediated OGD\/R-Induced Mitochondrial Dysfunction, Oxidative Stress, and Autophagy in Microglia and Neurons","volume":"192","author":"Long","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41392-024-01735-1","article-title":"Extracellular Vesicles as Tools and Targets in Therapy for Diseases","volume":"9","author":"Kumar","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"102226","DOI":"10.1016\/j.molmet.2025.102226","article-title":"Effects of Beta-Catenin Deficiency on Adipose Tissue Physiology","volume":"100","author":"Uranga","year":"2025","journal-title":"Mol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.cmet.2020.11.008","article-title":"Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity","volume":"33","author":"Brestoff","year":"2021","journal-title":"Cell Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1016\/j.cmet.2021.08.002","article-title":"Extracellular Vesicle-Based Interorgan Transport of Mitochondria from Energetically Stressed Adipocytes","volume":"33","author":"Crewe","year":"2021","journal-title":"Cell Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.cmet.2022.02.016","article-title":"Ejection of Damaged Mitochondria and Their Removal by Macrophages Ensure Efficient Thermogenesis in Brown Adipose Tissue","volume":"34","author":"Rosina","year":"2022","journal-title":"Cell Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115732","DOI":"10.1016\/j.celrep.2025.115732","article-title":"Exploring Adipose Tissue-Derived Extracellular Vesicles in Inter-Organ Crosstalk: Implications for Metabolic Regulation and Adipose Tissue Function","volume":"44","author":"Scherer","year":"2025","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.cmet.2022.08.004","article-title":"Extracellular Vesicles Mediate the Communication of Adipose Tissue with Brain and Promote Cognitive Impairment Associated with Insulin Resistance","volume":"34","author":"Wang","year":"2022","journal-title":"Cell Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e13339","DOI":"10.1111\/apha.13339","article-title":"Adipocyte-Derived Extracellular Vesicles Modulate Appetite and Weight through MTOR Signalling in the Hypothalamus","volume":"228","author":"Gao","year":"2020","journal-title":"Acta Physiologica"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Banks, W.A., Sharma, P., Bullock, K.M., Hansen, K.M., Ludwig, N., and Whiteside, T.L. (2020). Transport of Extracellular Vesicles across the Blood-Brain Barrier: Brain Pharmacokinetics and Effects of Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124407"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Batabyal, R.A., Bansal, A., Cechinel, L.R., Authelet, K., Goldberg, M., Nadler, E., Keene, C.D., Jayadev, S., Domoto-Reilly, K., and Li, G. (2023). Adipocyte-Derived Small Extracellular Vesicles from Patients with Alzheimer Disease Carry MiRNAs Predicted to Target the CREB Signaling Pathway in Neurons. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241814024"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e70603","DOI":"10.1002\/alz.70603","article-title":"Decoding Adipose-Brain Crosstalk: Distinct Lipid Cargo in Human Adipose-Derived Extracellular Vesicles Modulates Amyloid Aggregation in Alzheimer\u2019s Disease","volume":"21","author":"Yang","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.metabol.2018.11.005","article-title":"Obesity and Dyslipidemia","volume":"92","author":"Vekic","year":"2019","journal-title":"Metabolism"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1172\/JCI77812","article-title":"The Pathogenesis of Insulin Resistance: Integrating Signaling Pathways and Substrate Flux","volume":"126","author":"Samuel","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s13679-023-00518-z","article-title":"Obesity and Dyslipidemia: A Review of Current Evidence","volume":"12","author":"Vekic","year":"2023","journal-title":"Curr. Obes. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Maia, M.A., and Sousa, E. (2019). BACE-1 and \u03b3-Secretase as Therapeutic Targets for Alzheimer\u2019s Disease. Pharmaceuticals, 12.","DOI":"10.3390\/ph12010041"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.nbd.2007.10.005","article-title":"Cholesterol Retention in Alzheimer\u2019s Brain Is Responsible for High \u03b2- and \u03b3-Secretase Activities and A\u03b2 Production","volume":"29","author":"Xiong","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/alzrt135","article-title":"Apolipoprotein E, Amyloid-\u00df Clearance and Therapeutic Opportunities in Alzheimer\u2019s Disease","volume":"4","author":"Kline","year":"2012","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9317","DOI":"10.1126\/sciadv.adc9317","article-title":"Brain Lipidomics: From Functional Landscape to Clinical Significance","volume":"8","author":"Yoon","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ncb1313","article-title":"Regulation of Cholesterol and Sphingomyelin Metabolism by Amyloid-Beta and Presenilin","volume":"7","author":"Grimm","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.neurobiolaging.2008.05.010","article-title":"Deregulation of Sphingolipid Metabolism in Alzheimer\u2019s Disease","volume":"31","author":"He","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.neuron.2014.02.027","article-title":"Soluble A\u03b2 Oligomers Are Rapidly Sequestered from Brain ISF in Vivo and Bind GM1 Ganglioside on Cellular Membranes","volume":"82","author":"Hong","year":"2014","journal-title":"Neuron"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Savulescu-Fiedler, I., Dorobantu-Lungu, L.R., Dragosloveanu, S., Benea, S.N., Dragosloveanu, C.D.M., Caruntu, A., Scheau, A.E., Caruntu, C., and Scheau, C. (2025). The Cross-Talk Between the Peripheral and Brain Cholesterol Metabolisms. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47020115"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s11011-017-0015-3","article-title":"Cholesterol as a Modifying Agent of the Neurovascular Unit Structure and Function under Physiological and Pathological Conditions","volume":"32","author":"Czuba","year":"2017","journal-title":"Metab. Brain Dis."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Budny, V., Kn\u00f6pfli, Y., Meier, D., Z\u00fcrcher, K., Bodenmann, C., Peter, S.L., M\u00fcller, T., Tardy, M., Cortijo, C., and Tackenberg, C. (2024). APOE4 Increases Energy Metabolism in APOE-Isogenic IPSC-Derived Neurons. Cells, 13.","DOI":"10.1101\/2024.06.03.597106"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3236","DOI":"10.1007\/s12035-016-9885-3","article-title":"Phosphoinositides: Two-Path Signaling in Neuronal Response to Oligomeric Amyloid \u03b2 Peptide","volume":"54","author":"Uranga","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1750-3639.2005.tb00513.x","article-title":"Neuroprotectin D1 (NPD1): A DHA-Derived Mediator That Protects Brain and Retina against Cell Injury-Induced Oxidative Stress","volume":"15","author":"Bazan","year":"2005","journal-title":"Brain Pathol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"S400","DOI":"10.1194\/jlr.R800068-JLR200","article-title":"Neuroprotectin D1-Mediated Anti-Inflammatory and Survival Signaling in Stroke, Retinal Degenerations, and Alzheimer\u2019s Disease","volume":"50","author":"Bazan","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.plipres.2011.06.001","article-title":"Glycerophospholipids and Glycerophospholipid-Derived Lipid Mediators: A Complex Meshwork in Alzheimer\u2019s Disease Pathology","volume":"50","author":"Frisardi","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"ref_80","first-page":"430","article-title":"Spatial-Temporal Lipidomics Reveals Dysregulated Lipid Metabolism in Mouse Brain during Alzheimer\u2019s Disease Progression","volume":"26","author":"Li","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"a040535","DOI":"10.1101\/cshperspect.a040535","article-title":"Glycolysis","volume":"13","author":"Chandel","year":"2021","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1600-0404.1996.tb05868.x","article-title":"Oxidative Metabolism Deficiencies in Brains of Patients with Alzheimer\u2019s Disease","volume":"165","author":"Hoyer","year":"1996","journal-title":"Acta Neurol. Scand. Suppl."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/978-1-4419-8969-7_8","article-title":"Causes and Consequences of Disturbances of Cerebral Glucose Metabolism in Sporadic Alzheimer Disease: Therapeutic Implications","volume":"541","author":"Hoyer","year":"2004","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"101234","DOI":"10.1016\/j.molmet.2021.101234","article-title":"The Brain as an Insulin-Sensitive Metabolic Organ","volume":"52","author":"Milstein","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1177\/193229680800200619","article-title":"Alzheimer\u2019s Disease Is Type 3 Diabetes-Evidence Reviewed","volume":"2","author":"Wands","year":"2008","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kciuk, M., Kruczkowska, W., Galeziewska, J., Wanke, K., Kaluzinska-Kolat, Z., Aleksandrowicz, M., and Kontek, R. (2024). Alzheimer\u2019s Disease as Type 3 Diabetes: Understanding the Link and Implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252211955"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1055\/s-2007-1014893","article-title":"Enzyme Activities of Hepatic Glucose Utilization in the Fed and Fasting Genetically Obese Mouse at 4\u20135 Months of Age","volume":"16","author":"Hron","year":"1984","journal-title":"Horm. Metab. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/0026-0495(76)90001-9","article-title":"Enzymes Related to Lipogenesis in the Adipose Tissue of Obese Subjects","volume":"25","author":"Belfiore","year":"1976","journal-title":"Metabolism"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"E1039","DOI":"10.1152\/ajpendo.2000.279.5.E1039","article-title":"Lipid Oxidation Is Reduced in Obese Human Skeletal Muscle","volume":"279","author":"Kim","year":"2000","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Park, S.S., and Seo, Y.K. (2020). Excess Accumulation of Lipid Impairs Insulin Sensitivity in Skeletal Muscle. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061949"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s11684-013-0262-6","article-title":"Mechanisms of Insulin Resistance in Obesity","volume":"7","author":"Ye","year":"2013","journal-title":"Front. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s41586-025-09072-1","article-title":"CoQ Imbalance Drives Reverse Electron Transport to Disrupt Liver Metabolism","volume":"643","author":"Goncalves","year":"2025","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1172\/JCI59903","article-title":"Demonstrated Brain Insulin Resistance in Alzheimer\u2019s Disease Patients Is Associated with IGF-1 Resistance, IRS-1 Dysregulation, and Cognitive Decline","volume":"122","author":"Talbot","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41392-024-01839-8","article-title":"Mitochondrial Dysfunction: Mechanisms and Advances in Therapy","volume":"9","author":"Zong","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e2107022118","DOI":"10.1073\/pnas.2107022118","article-title":"Brain Power","volume":"118","author":"Balasubramanian","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.phrs.2018.03.010","article-title":"VDAC1, Mitochondrial Dysfunction, and Alzheimer\u2019s Disease","volume":"131","author":"Gupta","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.3233\/JAD-170585","article-title":"Mitochondria and Mitochondrial Cascades in Alzheimer\u2019s Disease","volume":"62","author":"Swerdlow","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.mehy.2003.12.045","article-title":"A \u201cMitochondrial Cascade Hypothesis\u201d for Sporadic Alzheimer\u2019s Disease","volume":"63","author":"Swerdlow","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Patro, S., Ratna, S., Yamamoto, H.A., Ebenezer, A.T., Ferguson, D.S., Kaur, A., McIntyre, B.C., Snow, R., and Solesio, M.E. (2021). ATP Synthase and Mitochondrial Bioenergetics Dysfunction in Alzheimer\u2019s Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011185"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"101639","DOI":"10.1016\/j.arr.2022.101639","article-title":"Oxidative Stress and Antioxidant Defenses in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis","volume":"79","author":"Nantachai","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"18725","DOI":"10.1038\/srep18725","article-title":"Altered Brain Energetics Induces Mitochondrial Fission Arrest in Alzheimer\u2019s Disease","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1002\/oby.23374","article-title":"Beyond Appetite Regulation: Targeting Energy Expenditure, Fat Oxidation, and Lean Mass Preservation for Sustainable Weight Loss","volume":"30","author":"Christoffersen","year":"2022","journal-title":"Obesity"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Nava-Aguilar, V., Ruiz-Ramirez, A., Ceja-Galicia, Z.A., de la Luz Hernandez Esquivel, M., Cristobal Garcia, M., Carbo Zabala, R., Cardoso-Saldana, G.C., and El-Hafidi, M. (2025). Mitochondrial ATP Biosynthesis Is Negatively Associated with FFA in Cardiac and Skeletal Muscle During the Development of Obesity in a Rodent Model. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26188768"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"734","DOI":"10.18632\/aging.100505","article-title":"Nutrient Availability Links Mitochondria, Apoptosis, and Obesity","volume":"4","author":"Pintus","year":"2012","journal-title":"Aging"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1080\/1028415X.2025.2546950","article-title":"Obesity and Alzheimer s Disease: Unraveling the Impact of Chronic Consumption of High-Fat or High-Sucrose Diets on Neurodegeneration and Mitochondrial Dysfunction","volume":"29","author":"Zazueta","year":"2026","journal-title":"Nutr. Neurosci."},{"key":"ref_106","first-page":"2553","article-title":"Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer\u2019s Disease: Mechanisms, Implications, and Potential Therapies","volume":"16","author":"Mohan","year":"2025","journal-title":"Aging Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1089\/ars.2012.4875","article-title":"Mitochondrial Fatty Acid Oxidation in Obesity","volume":"19","author":"Serra","year":"2013","journal-title":"Antioxid. Redox Signal"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Bang, S., Choi, S.H., and Jeong, S.M. (2025). Beyond Bioenergetics: Emerging Roles of Mitochondrial Fatty Acid Oxidation in Stress Response and Aging. Cells, 14.","DOI":"10.3390\/cells14241956"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"102726","DOI":"10.1016\/j.arr.2025.102726","article-title":"Unraveling the Mystery of Citrate Transporters in Alzheimer\u2019s Disease: An Updated Review","volume":"107","author":"Mukherjee","year":"2025","journal-title":"Ageing Res. Rev."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"S453","DOI":"10.3233\/JAD-220514","article-title":"The Novel Role of Mitochondrial Citrate Synthase and Citrate in the Pathophysiology of Alzheimer\u2019s Disease","volume":"94","author":"Chhimpa","year":"2023","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.redox.2017.04.010","article-title":"Platelet Cytochrome Oxidase and Citrate Synthase Activities in APOE Epsilon4 Carrier and Non-Carrier Alzheimer\u2019s Disease Patients","volume":"12","author":"Wilkins","year":"2017","journal-title":"Redox Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.mito.2019.07.013","article-title":"Activities of Mitochondrial Respiratory Chain Complexes in Platelets of Patients with Alzheimer\u2019s Disease and Depressive Disorder","volume":"48","author":"Fisar","year":"2019","journal-title":"Mitochondrion"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"E262","DOI":"10.1152\/ajpendo.00271.2013","article-title":"Metabolic Remodeling of White Adipose Tissue in Obesity","volume":"307","author":"Cummins","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_114","first-page":"826027","article-title":"Obesity Affects Mitochondrial Citrate Synthase in Human Omental Adipose Tissue","volume":"2013","author":"Christe","year":"2013","journal-title":"ISRN Obes."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1152\/physiolgenomics.00066.2010","article-title":"H55N Polymorphism as a Likely Cause of Variation in Citrate Synthase Activity of Mouse Skeletal Muscle","volume":"42A","author":"Ratkevicius","year":"2010","journal-title":"Physiol. Genom."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"649","DOI":"10.3233\/JAD-142052","article-title":"Lymphocytic Mitochondrial Aconitase Activity Is Reduced in Alzheimer\u2019s Disease and Mild Cognitive Impairment","volume":"44","author":"Mangialasche","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/ana.20474","article-title":"Mitochondrial Abnormalities in Alzheimer Brain: Mechanistic Implications","volume":"57","author":"Bubber","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/s41392-024-01812-5","article-title":"A Positive Feedback Inhibition of Isocitrate Dehydrogenase 3beta on Paired-Box Gene 6 Promotes Alzheimer-like Pathology","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"6688","DOI":"10.1096\/fj.201903224RR","article-title":"Mitochondrial Aconitase Controls Adipogenesis through Mediation of Cellular ATP Production","volume":"34","author":"Chen","year":"2020","journal-title":"FASEB J."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Fernandes, J., Szweda, L.I., and Kinter, M. (2012). Enhanced Cardiac Fatty Acid Utilization Induced by High Dietary Fat: A Potential Regulatory Role for Mitochondrial Aconitase. BMC Proc., 6.","DOI":"10.1186\/1753-6561-6-S3-P15"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1093\/jalm\/jfaf124","article-title":"Differential NADP-Dependent Isocitrate Dehydrogenases Expression in Metabolically Healthy Obesity vs Metabolic Syndrome: A Probable Predictive Biomarker for Metabolic Deterioration","volume":"10","author":"Watany","year":"2025","journal-title":"J. Appl. Lab. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e13059","DOI":"10.1111\/acel.13059","article-title":"Dietary Alpha-Ketoglutarate Promotes Beige Adipogenesis and Prevents Obesity in Middle-Aged Mice","volume":"19","author":"Tian","year":"2020","journal-title":"Aging Cell"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Jia, D., Wang, F., and Yu, H. (2023). Systemic Alterations of Tricarboxylic Acid Cycle Enzymes in Alzheimer\u2019s Disease. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1206688"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41467-021-27572-2","article-title":"Altered Succinylation of Mitochondrial Proteins, APP and Tau in Alzheimer\u2019s Disease","volume":"13","author":"Yang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1046\/j.1471-4159.1995.65062585.x","article-title":"Suppression of Mitochondrial Succinate Dehydrogenase, a Primary Target of Beta-Amyloid, and Its Derivative Racemized at Ser Residue","volume":"65","author":"Kaneko","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Yang, Y., Luo, L., Li, Y., Shi, X., Li, C., Chai, J., Jiang, S., and Zheng, R. (2024). Succinic Acid Improves the Metabolism of High-Fat Diet-Induced Mice and Promotes White Adipose Browning. Nutrients, 16.","DOI":"10.3390\/nu16223828"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1073\/pnas.1914553117","article-title":"Scd1 Controls de Novo Beige Fat Biogenesis through Succinate-Dependent Regulation of Mitochondrial Complex II","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/s41586-018-0353-2","article-title":"Accumulation of Succinate Controls Activation of Adipose Tissue Thermogenesis","volume":"560","author":"Mills","year":"2018","journal-title":"Nature"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"e952","DOI":"10.1038\/tp.2016.194","article-title":"A Targeted Proteomic Multiplex CSF Assay Identifies Increased Malate Dehydrogenase and Other Neurodegenerative Biomarkers in Individuals with Alzheimer\u2019s Disease Pathology","volume":"6","author":"Paterson","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.freeradbiomed.2019.12.037","article-title":"Fumarate and Oxidative Stress Synergize to Promote Stability of C\/EBP Homologous Protein in the Adipocyte","volume":"148","author":"Manuel","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.2337\/db16-0136","article-title":"Adipose-Specific Deficiency of Fumarate Hydratase in Mice Protects Against Obesity, Hepatic Steatosis, and Insulin Resistance","volume":"65","author":"Yang","year":"2016","journal-title":"Diabetes"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"102616","DOI":"10.1016\/j.xcrm.2026.102616","article-title":"Hypothalamic Malate Dehydrogenase 2 Modulates Systemic Glucose Metabolism through Oxytocin-Mediated Thermogenesis","volume":"7","author":"Yao","year":"2026","journal-title":"Cell Rep. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.scr.2018.01.019","article-title":"Oxidative Stress and Altered Mitochondrial Protein Expression in the Absence of Amyloid-Beta and Tau Pathology in IPSC-Derived Neurons from Sporadic Alzheimer\u2019s Disease Patients","volume":"27","author":"Birnbaum","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00259-014-2919-z","article-title":"Cortical Hypermetabolism in MCI Subjects: A Compensatory Mechanism?","volume":"42","author":"Ashraf","year":"2015","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1038\/s41380-023-02289-4","article-title":"Mitochondrial Hypermetabolism Precedes Impaired Autophagy and Synaptic Disorganization in App Knock-in Alzheimer Mouse Models","volume":"28","author":"Naia","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Radovic, M., Gartzke, L.P., Wink, S.E., van der Kleij, J.A., Politiek, F.A., and Krenning, G. (2025). Targeting the Electron Transport System for Enhanced Longevity. Biomolecules, 15.","DOI":"10.3390\/biom15050614"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13024-021-00448-1","article-title":"Mitochondrial Complex I Abnormalities Is Associated with Tau and Clinical Symptoms in Mild Alzheimer\u2019s Disease","volume":"16","author":"Terada","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1212\/WNL.40.8.1302","article-title":"Cytochrome Oxidase Deficiency in Alzheimer\u2019s Disease","volume":"40","author":"Parker","year":"1990","journal-title":"Neurology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1046\/j.1471-4159.1994.63062179.x","article-title":"Cortical Cytochrome Oxidase Activity Is Reduced in Alzheimer\u2019s Disease","volume":"63","author":"Mutisya","year":"1994","journal-title":"J. Neurochem."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1523\/JNEUROSCI.4276-04.2005","article-title":"Copper-Dependent Inhibition of Human Cytochrome c Oxidase by a Dimeric Conformer of Amyloid-Beta1-42","volume":"25","author":"Crouch","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.mito.2006.10.004","article-title":"Impaired Platelet Mitochondrial Activity in Alzheimer\u2019s Disease and Mild Cognitive Impairment","volume":"6","author":"Valla","year":"2006","journal-title":"Mitochondrion"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1089\/met.2015.0095","article-title":"Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies","volume":"13","author":"Manna","year":"2015","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1113\/EP087278","article-title":"Mitochondrial ATP Synthase \u03b2-Subunit Production Rate and ATP Synthase Specific Activity Are Reduced in Skeletal Muscle of Humans with Obesity","volume":"104","author":"Tran","year":"2019","journal-title":"Exp. Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"bqac018","DOI":"10.1210\/endocr\/bqac018","article-title":"Adipose Mitochondrial Complex I Deficiency Modulates Inflammation and Glucose Homeostasis in a Sex-Dependent Manner","volume":"163","author":"Choi","year":"2022","journal-title":"Endocrinology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1016\/j.celrep.2016.08.041","article-title":"Role of Mitochondrial Complex IV in Age-Dependent Obesity","volume":"16","author":"Li","year":"2016","journal-title":"Cell Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.exger.2010.01.003","article-title":"The Sites and Topology of Mitochondrial Superoxide Production","volume":"45","author":"Brand","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1007\/PL00000661","article-title":"Decreased Levels of Complex III Core Protein 1 and Complex V Beta Chain in Brains from Patients with Alzheimer\u2019s Disease and Down Syndrome","volume":"57","author":"Kim","year":"2000","journal-title":"Cell Mol. Life Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"2300","DOI":"10.1038\/s42255-025-01390-y","article-title":"Mitochondrial Complex III-Derived ROS Amplify Immunometabolic Changes in Astrocytes and Promote Dementia Pathology","volume":"7","author":"Barnett","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.cmet.2011.08.007","article-title":"Mitochondrial Complex III ROS Regulate Adipocyte Differentiation","volume":"14","author":"Tormos","year":"2011","journal-title":"Cell Metab."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"930","DOI":"10.2174\/1567205013666160314150856","article-title":"Mitochondrial Respiration in the Platelets of Patients with Alzheimer\u2019s Disease","volume":"13","author":"Fisar","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Berdun, R., Obis, E., Mota-Martorell, N., Bassols, A., Valent, D., Serrano, J.C.E., Martin-Gari, M., Rodriguez-Palmero, M., Moreno-Munoz, J.A., and Tibau, J. (2024). High-Fat Diet-Induced Obesity Increases Brain Mitochondrial Complex I and Lipoxidation-Derived Protein Damage. Antioxidants, 13.","DOI":"10.3390\/antiox13020161"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nature19774","article-title":"The Architecture of Respiratory Supercomplexes","volume":"537","author":"Letts","year":"2016","journal-title":"Nature"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1042\/CS20210506","article-title":"Targeting Skeletal Muscle Mitochondrial Health in Obesity","volume":"136","author":"Pileggi","year":"2022","journal-title":"Clin. Sci."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Tamagno, E., Guglielmotto, M., Vasciaveo, V., and Tabaton, M. (2021). Oxidative Stress and Beta Amyloid in Alzheimer\u2019s Disease. Which Comes First: The Chicken or the Egg?. Antioxidants, 10.","DOI":"10.3390\/antiox10091479"},{"key":"ref_155","first-page":"151979","article-title":"Tau Hyperphosphorylation and Oxidative Stress, a Critical Vicious Circle in Neurodegenerative Tauopathies?","volume":"2015","year":"2015","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1172\/JCI21625","article-title":"Increased Oxidative Stress in Obesity and Its Impact on Metabolic Syndrome","volume":"114","author":"Furukawa","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11154-013-9271-7","article-title":"Roles of Adiponectin and Oxidative Stress in Obesity-Associated Metabolic and Cardiovascular Diseases","volume":"15","author":"Matsuda","year":"2014","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/j.pbj.0000000000000059","article-title":"Influence of Gut Microbiota Dysbiosis on Brain Function: A Systematic Review","volume":"5","author":"Almeida","year":"2020","journal-title":"Porto Biomed. J."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"101982","DOI":"10.1016\/j.xcrm.2025.101982","article-title":"The Gut Microbiota-Immune-Brain Axis: Therapeutic Implications","volume":"6","author":"Moloney","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"4586","DOI":"10.1073\/pnas.1000097107","article-title":"Composition, Variability, and Temporal Stability of the Intestinal Microbiota of the Elderly","volume":"108","author":"Claesson","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bbi.2017.02.004","article-title":"Revisiting Metchnikoff: Age-Related Alterations in Microbiota-Gut-Brain Axis in the Mouse","volume":"65","author":"Scott","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"G727","DOI":"10.1152\/ajpgi.00174.2024","article-title":"The Gut Microbiota as a Link between Alzheimer\u2019s Disease and Obesity","volume":"327","author":"Alvarez","year":"2024","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"111198","DOI":"10.1016\/j.nut.2021.111198","article-title":"Sodium Acetate, Propionate, and Butyrate Reduce Fat Accumulation in Mice via Modulating Appetite and Relevant Genes","volume":"87\u201388","author":"Jiao","year":"2021","journal-title":"Nutrition"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3233\/JAD-190120","article-title":"Sodium Butyrate Reduces Brain Amyloid-\u03b2 Levels and Improves Cognitive Memory Performance in an Alzheimer\u2019s Disease Transgenic Mouse Model at an Early Disease Stage","volume":"74","author":"Fernando","year":"2020","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e111515","DOI":"10.15252\/embj.2022111515","article-title":"Gut Microbiota Regulates Blood-cerebrospinal Fluid Barrier Function and A\u03b2 Pathology","volume":"42","author":"Xie","year":"2023","journal-title":"EMBO J."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez-Cuesta, S., Lozano Garc\u00eda, N., Rodr\u00edguez-Fern\u00e1ndez, S., Fern\u00e1ndez-Avila, A.I., Bermejo, J., Fern\u00e1ndez-Avil\u00e9s, F., Mu\u00f1oz, P., Bouza, E., and Reigadas, E. (2024). Impact of the Mediterranean Diet on the Gut Microbiome of a Well-Defined Cohort of Healthy Individuals. Nutrients, 16.","DOI":"10.3390\/nu16060793"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13024-023-00595-7","article-title":"The Gut Microbiome in Alzheimer\u2019s Disease: What We Know and What Remains to Be Explored","volume":"18","author":"Chandra","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1136\/gutjnl-2018-317431","article-title":"Transfer of a Healthy Microbiota Reduces Amyloid and Tau Pathology in an Alzheimer\u2019s Disease Animal Model","volume":"69","author":"Kim","year":"2020","journal-title":"Gut"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s12276-023-01146-2","article-title":"Current Understanding of the Alzheimer\u2019s Disease-Associated Microbiome and Therapeutic Strategies","volume":"56","author":"Seo","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"eabo2984","DOI":"10.1126\/scitranslmed.abo2984","article-title":"Gut Microbiome Composition May Be an Indicator of Preclinical Alzheimer\u2019s Disease","volume":"15","author":"Ferreiro","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/s41422-019-0216-x","article-title":"Sodium Oligomannate Therapeutically Remodels Gut Microbiota and Suppresses Gut Bacterial Amino Acids-Shaped Neuroinflammation to Inhibit Alzheimer\u2019s Disease Progression","volume":"29","author":"Wang","year":"2019","journal-title":"Cell Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"101317","DOI":"10.1016\/j.arr.2021.101317","article-title":"Inflammatory Pathways in Alzheimer\u2019s Disease Mediated by Gut Microbiota","volume":"68","author":"Qian","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S2468-1253(17)30147-4","article-title":"The Microbiota\u2013Gut\u2013Brain Axis in Obesity","volume":"2","author":"Schellekens","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"H740","DOI":"10.1152\/ajpheart.00736.2020","article-title":"Obesity-Induced Cognitive Impairment in Older Adults: A Microvascular Perspective","volume":"320","author":"Balasubramanian","year":"2021","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Pinart, M., D\u00f6tsch, A., Schlicht, K., Laudes, M., Bouwman, J., Forslund, S.K., Pischon, T., and Nimptsch, K. (2021). Gut Microbiome Composition in Obese and Non-Obese Persons: A Systematic Review and Meta-Analysis. Nutrients, 14.","DOI":"10.3390\/nu14010012"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2605879","DOI":"10.1080\/29933935.2025.2605879","article-title":"Obesity-Associated Gut Microbiome Influences Diet-Induced Metabolic and Cognitive Outcomes in Older Adults","volume":"3","author":"Patoine","year":"2026","journal-title":"Gut Microbes Rep."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"13537","DOI":"10.1038\/s41598-017-13601-y","article-title":"Gut Microbiome Alterations in Alzheimer\u2019s Disease","volume":"7","author":"Vogt","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/8\/672\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:34:11Z","timestamp":1775817251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/8\/672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":177,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cells15080672"],"URL":"https:\/\/doi.org\/10.3390\/cells15080672","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}