Adiponectin: a potential target for obesity-associated Alzheimer's disease.

Publisher: Springer Country of Publication: United States NLM ID: 8610370 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7365 (Electronic) Linking ISSN: 08857490 NLM ISO Abbreviation: Metab Brain Dis Subsets: MEDLINE

Publication: 2005- : Amsterdam : Springer
Original Publication: New York : Plenum, c1986-

Adiponectin/*physiology ; Alzheimer Disease/*drug therapy ; Obesity/*complications; Adiponectin/agonists ; Adiponectin/therapeutic use ; Alzheimer Disease/etiology ; Animals ; Humans ; Insulin/physiology ; Leptin/physiology ; Obesity/drug therapy ; Signal Transduction/physiology

Obesity and dementia are two growing problems worldwide. Obesity act as a crucial risk factor for various diseases including Alzheimer's disease (AD). Several preclinical studies showed that middle-age obesity can be act as a possible feature of mild cognitive impairment in later years. Some studies have also demonstrated that a high-fat diet causes AD pathology, including extracellular amyloid-beta accumulation, hyperphosphorylation of tau, and cognition impairment. The correlation and molecular mechanism related to obesity-associated AD needs to be better evaluated. Presently, obesity results in an altered expression of several hormones, growth factors, and adipokines. Multiple signaling pathways such as leptin, insulin, adiponectin, and glutamate are involved to regulate vital functions in the brain and act as neuroprotective mediators for AD in a normal state. In obesity, altered adiponectin (APN) level and its associated downstream pathway could result in multiple signaling pathway disruption. Presently, Adiponectin and its inducers or agonist are considered as potential therapeutics for obesity-associated AD. This review mainly focuses on the pleiotropic effects of adiponectin and its potential to treat obesity-associated AD.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Afzal M, Redha A, AlHasan R (2019) Anthocyanins Potentially Contribute to Defense against Alzheimer’s Disease. Molecules 24:4255. https://doi.org/10.3390/molecules24234255. (PMID: 10.3390/molecules242342556930593)
Albanese E, Launer LJ, Egger M, Prince MJ, Giannakopoulos P, Wolters FJ, Egan K (2017) Body mass index in midlife and dementia: systematic review and meta‐regression analysis of 589,649 men and women followed in longitudinal studies. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring 8(1):165–178. https://doi.org/10.1016/j.dadm.2017.05.007.
Ali T, Yoon GH, Shah SA, Lee HY, Kim MO (2015) Osmotin attenuates amyloid beta-induced memory impairment, tau phosphorylation and neurodegeneration in the mouse hippocampus. Sci Rep 5:11708. https://doi.org/10.1038/srep11708. (PMID: 10.1038/srep11708261187574484370)
Ancelin ML, Carrière I, Barberger-Gateau P, Auriacombe S, Rouaud O, Fourlanos S, Berr C, Dupuy AM, Ritchie K (2012) Lipid lowering agents, cognitive decline, and dementia: the three-city study. J Alzheimers Dis 30:629–637. https://doi.org/10.3233/JAD-2012-120064. (PMID: 10.3233/JAD-2012-120064224513173743740)
Becic T, Studenik C, Hoffmann G (2018) Exercise Increases Adiponectin and Reduces Leptin Levels in Prediabetic and Diabetic Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Med Sci (basel) 6:97. https://doi.org/10.3390/medsci6040097. (PMID: 10.3390/medsci6040097)
Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM (2014) Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer’s disease. Front Endocrinol 5:161. https://doi.org/10.3389/fendo.2014.00161. (PMID: 10.3389/fendo.2014.00161)
Bloemer J, Pinky PD, Govindarajulu M, Hong H, Judd R, Amin RH, Moore T, Dhanasekaran M, Reed MN, Suppiramaniam V (2018) Role of adiponectin in central nervous system disorders. Neural Plast 2018:4593530. https://doi.org/10.1155/2018/4593530.
Bray GA, Heisel WE, Afshin A, Jensen MD, Dietz WH, Long M, Kushner RF, Daniels SR, Wadden TA, Tsai AG, Hu FB, Jakicic JM, Ryan DH, Wolfe BM, Inge TH (2018) The science of obesity management: an endocrine society scientific statement. Endocr Rev 39(2):79–132.  https://doi.org/10.1210/er.2017-00253.
Chen R, Shu Y, Zeng Y (2020) Links Between Adiponectin and Dementia: From Risk Factors to Pathophysiology. Front Aging Neurosci 11:356. https://doi.org/10.3389/fnagi.2019.00356. (PMID: 10.3389/fnagi.2019.00356319698136960116)
Cheng H, Wang M, Li JL, Cairns NJ, Han X (2013) Specific changes of sulfatide levels in individuals with pre-clinical Alzheimer’s disease: an early event in disease pathogenesis. J Neurochem 127:733–738. https://doi.org/10.1111/jnc.12368. (PMID: 10.1111/jnc.1236823865640)
Chopra I, Li HF, Wang H, Webster KA (2012) Phosphorylation of the insulin receptor by AMP-activated protein kinase (AMPK) promotes ligand-independent activation of the insulin signalling pathway in rodent muscle. Diabetologia 55:783–794. https://doi.org/10.1007/s00125-011-2407-y. (PMID: 10.1007/s00125-011-2407-y22207502)
Danat IM, Clifford A, Partridge M, Zhou W, Bakre AT, Chen A, McFeeters D, Smith T, Wan Y, Copeland J, Anstey KJ, Chen R (2019) Impacts of Overweight and Obesity in Older Age on the Risk of Dementia: A Systematic Literature Review and a Meta-Analysis. J Alzheimers Dis 70:S87–S99. https://doi.org/10.3233/JAD-180763. (PMID: 10.3233/JAD-180763306895746700617)
Dorrance A, Matin N, Pires P (2014) The effects of obesity on the cerebral vasculature. Curr Vasc Pharmacol 12(3):462–472.  https://doi.org/10.2174/1570161112666140423222411.
Duan Y, Zeng L, Zheng C, Song B, Li F, Kong X, Xu K (2018) Inflammatory links between high fat diets and diseases. Front Immunol 9:2649. https://doi.org/10.3389/fimmu.2018.02649.
Dumont M, Stack C, Elipenahli C, Jainuddin S, Gerges M, Starkova N, Calingasan NY, Yang L, Tampellini D, Starkov AA, Chan RB, Di Paolo G, Pujol A, Beal MF (2012) Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice. Hum Mol Genet 21:5091–5105. https://doi.org/10.1093/hmg/dds355. (PMID: 10.1093/hmg/dds355229222303490516)
Ferreira L, Fernandes CS, Vieira M, De Felice FG (2018) Insulin Resistance in Alzheimer’s Disease. Front Neurosci 12:830. https://doi.org/10.3389/fnins.2018.00830. (PMID: 10.3389/fnins.2018.00830305422576277874)
Ferreira ST, Lourenco MV, Oliveira MM, De Felice FG (2015) Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer’s disease. Front Cell Neurosci 9:191. https://doi.org/10.3389/fncel.2015.00191. (PMID: 10.3389/fncel.2015.00191260747674443025)
Forny-Germano L, De Felice FG, Vieira M (2019) The Role of Leptin and Adiponectin in Obesity-Associated Cognitive Decline and Alzheimer’s Disease. Front Neurosci 12:1027. https://doi.org/10.3389/fnins.2018.01027. (PMID: 10.3389/fnins.2018.01027306929056340072)
Fruh SM (2017) Obesity: Risk factors, complications, and strategies for sustainable long-term weight management. J Am Assoc Nurse Pract 29:S3–S14. https://doi.org/10.1002/2327-6924.12510. (PMID: 10.1002/2327-6924.12510290245536088226)
Ide K, Matsuoka N, Yamada H, Furushima D, Kawakami K (2018) Effects of Tea Catechins on Alzheimer’s Disease: Recent Updates and Perspectives. Molecules 23:2357. https://doi.org/10.3390/molecules23092357. (PMID: 10.3390/molecules230923576225145)
Imamura T, Tsuruma K, Inoue Y, Otsuka T, Ohno Y, Ogami S, Yamane S, Shimazawa M, Hara H (2017) Rimonabant, a selective cannabinoid 1 receptor antagonist, protects against light-induced retinal degeneration in vitro and in vivo. Eur J Pharmacol 803:78–83. https://doi.org/10.1016/j.ejphar.2017.03.018. (PMID: 10.1016/j.ejphar.2017.03.01828315677)
Irving AJ, Harvey J (2013) Leptin regulation of hippocampal synaptic function in health and disease. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 369:20130155. https://doi.org/10.1098/rstb.2013.0155 .
Iwabu M, Okada-Iwabu M, Yamauchi T, Kadowaki T (2019) Adiponectin/AdipoR Research and Its Implications for Lifestyle-Related Diseases. Front Cardiovasc Med 6:116. https://doi.org/10.3389/fcvm.2019.00116. (PMID: 10.3389/fcvm.2019.00116314751606703139)
Jais A, Brüning JC (2017) Hypothalamic inflammation in obesity and metabolic disease. J Clin Investig 127:24–32. https://doi.org/10.1172/JCI88878. (PMID: 10.1172/JCI88878280453965199695)
Jasinski-Bergner S, Büttner M, Quandt D, Seliger B, Kielstein H (2017) Adiponectin and Its Receptors Are Differentially Expressed in Human Tissues and Cell Lines of Distinct Origin. Obes Facts 10:569–583. https://doi.org/10.1159/000481732. (PMID: 10.1159/000481732292073955836243)
Kausar S, Wang F, Cui H (2018) The Role of Mitochondria in Reactive Oxygen Species Generation and Its Implications for Neurodegenerative Diseases. Cells 7:274. https://doi.org/10.3390/cells7120274. (PMID: 10.3390/cells71202746316843)
Kim JY, Barua S, Jeong YJ, Lee JE (2020) Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer’s Disease. Int J Mol Sci 21:6419. https://doi.org/10.3390/ijms21176419. (PMID: 10.3390/ijms211764197504582)
Koenig AM, Mechanic-Hamilton D, Xie SX, Combs MF, Cappola AR, Xie L, Detre JA, Wolk DA, Arnold SE (2017) Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study. Alzheimer Dis Assoc Disord 31:107–113. https://doi.org/10.1097/WAD.0000000000000202. (PMID: 10.1097/WAD.0000000000000202285380885476214)
Kurochkin IV, Guarnera E, Berezovsky IN (2018) Insulin-Degrading Enzyme in the Fight against Alzheimer’s Disease. Trends Pharmacol Sci 39:49–58. https://doi.org/10.1016/j.tips.2017.10.008. (PMID: 10.1016/j.tips.2017.10.00829132916)
Lewerenz J, Maher P (2015) Chronic Glutamate Toxicity in Neurodegenerative Diseases-What is the Evidence? Front Neurosci 9:469. https://doi.org/10.3389/fnins.2015.00469. (PMID: 10.3389/fnins.2015.00469267337844679930)
Lloret A, Monllor P, Esteve D, Cervera-Ferri A, Lloret MA (2019) Obesity as a Risk Factor for Alzheimer’s Disease: Implication of Leptin and Glutamate. Front Neurosci 13:508. https://doi.org/10.3389/fnins.2019.00508. (PMID: 10.3389/fnins.2019.00508311912206540965)
Luchsinger JA, Gustafson DR (2009) Adiposity and Alzheimer’s disease. Curr Opin Clin Nutr Metab Care 12:15–21. https://doi.org/10.1097/MCO.0b013e32831c8c71. (PMID: 10.1097/MCO.0b013e32831c8c71190571822771208)
Mancuso P (2016) The role of adipokines in chronic inflammation. Immunotargets Ther 5:47–56. https://doi.org/10.2147/ITT.S73223. (PMID: 10.2147/ITT.S73223275290614970637)
Matioli M, Nitrini R (2015) Mechanisms linking brain insulin resistance to Alzheimer’s disease. Dementia & Neuropsychologia 9:96–102. https://doi.org/10.1590/1980-57642015DN92000003. (PMID: 10.1590/1980-57642015DN92000003)
McGuire MJ, Ishii M (2016) Leptin Dysfunction and Alzheimer’s Disease: Evidence from Cellular, Animal, and Human Studies. Cell Mol Neurobiol 36:203–217. https://doi.org/10.1007/s10571-015-0282-7. (PMID: 10.1007/s10571-015-0282-7269935094846558)
Mullins RJ, Diehl TC, Chia CW, Kapogiannis D (2017) Insulin Resistance as a Link between Amyloid-Beta and Tau Pathologies in Alzheimer’s Disease. Front Aging Neurosci 9:118. https://doi.org/10.3389/fnagi.2017.00118. (PMID: 10.3389/fnagi.2017.00118285156885413582)
Ng RC, Chan KH (2017) Potential Neuroprotective Effects of Adiponectin in Alzheimer’s Disease. Int J Mol Sci 18:592. https://doi.org/10.3390/ijms18030592. (PMID: 10.3390/ijms180305925372608)
Ng RC, Cheng OY, Jian M, Kwan JS, Ho PW, Cheng KK, Yeung PK, Zhou LL, Hoo RL, Chung SK, Xu A, Lam KS, Chan KH (2016) Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice. Mol Neurodegener 11:71. https://doi.org/10.1186/s13024-016-0136-x. (PMID: 10.1186/s13024-016-0136-x278841635123368)
Nguyen JCD, Killcross AS, Jenkins TA (2014) Obesity and cognitive decline: role of inflammation and vascular changes. Front Neurosci 8:375. https://doi.org/10.3389/fnins.2014.00375.
Nizami S, Hall-Roberts H, Warrier S, Cowley SA, Di Daniel E. (2019) Microglial inflammation and phagocytosis in Alzheimer's disease: Potential therapeutic targets. British j pharmacol 176:3515–3532. https://doi.org/10.1111/bph.14618 .
Otvos L Jr (2019) Potential Adiponectin Receptor Response Modifier Therapeutics. Front Endocrinol 10:539. https://doi.org/10.3389/fendo.2019.00539. (PMID: 10.3389/fendo.2019.00539)
Proia P, Di Liegro CM, Schiera G, Fricano A, Di Liegro I (2016) Lactate as a Metabolite and a Regulator in the Central Nervous System. Int J Mol Sci 17:1450. https://doi.org/10.3390/ijms17091450. (PMID: 10.3390/ijms170914505037729)
Purkayastha S, Cai D (2013) Disruption of neurogenesis by hypothalamic inflammation in obesity or aging. Rev Endocr Metab Disord 14:351–356. https://doi.org/10.1007/s11154-013-9279-z. (PMID: 10.1007/s11154-013-9279-z24158306)
Rizzo MR, Fasano R, Paolisso G (2020) Adiponectin and Cognitive Decline. Int J Mol Sci 21:2010. https://doi.org/10.3390/ijms21062010. (PMID: 10.3390/ijms210620107139651)
Ruan H, Dong LQ (2016) Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol 8:101–109. https://doi.org/10.1093/jmcb/mjw014. (PMID: 10.1093/jmcb/mjw014269930444816150)
Ryu J, Galan AK, Xin X, Dong F, Abdul-Ghani MA, Zhou L, Wang C, Li C, Holmes BM, Sloane LB, Austad SN, Guo S, Musi N, DeFronzo RA, Deng C, White MF, Liu F, Dong LQ (2014) APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor. Cell Rep 7:1227–1238. https://doi.org/10.1016/j.celrep.2014.04.006. (PMID: 10.1016/j.celrep.2014.04.006248138964380268)
Shah SA, Yoon GH, Chung SS, Abid MN, Kim TH, Lee HY, Kim MO (2017) Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer’s disease neuropathological deficits. Mol Psychiatry 22:407–416. https://doi.org/10.1038/mp.2016.23. (PMID: 10.1038/mp.2016.2327001618)
Song J, Choi SM, Kim BC (2017) Adiponectin Regulates the Polarization and Function of Microglia via PPAR-γ Signaling Under Amyloid β Toxicity. Front Cell Neurosci 11:64. https://doi.org/10.3389/fncel.2017.00064. (PMID: 10.3389/fncel.2017.00064283260175339235)
Tagarelli A, Piro A, Tagarelli G, Lagonia P, Quattrone, A. (2006) Alois Alzheimer: a hundred years after the discovery of the eponymous disorder. International j biomedic sci 2:196–204. PMID: 23674983; PMCID: PMC3614590.
Tamang HK, Timilsina U, Singh KP, Shrestha S, Pandey B, Basnet S, Waiba B, Shrestha U (2013) Assessment of adiponectin level in obese and lean Nepalese population and its possible correlation with lipid profile: A cross-sectional study. Indian Journal of Endocrinology and Metabolism 17:S349–S354. https://doi.org/10.4103/2230-8210.119618. (PMID: 10.4103/2230-8210.119618242512113830357)
Tan BL, Norhaizan ME, Liew WP, Sulaiman RH (2018) Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases. Front Pharmacol 9:1162. https://doi.org/10.3389/fphar.2018.01162. (PMID: 10.3389/fphar.2018.01162304054056204759)
Thundyil J, Pavlovski D, Sobey CG, Arumugam TV (2012) Adiponectin receptor signalling in the brain. Br J Pharmacol 165:313–327. https://doi.org/10.1111/j.1476-5381.2011.01560.x. (PMID: 10.1111/j.1476-5381.2011.01560.x217182993268187)
Velikova M, Doncheva D, Tashev R (2020) Effects of Rimonabant on active avoidance learning in bulbectomized rats. J of IMAB 26:2936–2941. https://doi.org/10.5272/jimab.2020261.2936. (PMID: 10.5272/jimab.2020261.2936)
Verdile G, Keane KN, Cruzat VF, Medic S, Sabale M, Rowles J, Wijesekara N, Martins RN, Fraser PE, Newsholme P (2015) Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer’s Disease. Mediators Inflamm 2015:105828. https://doi.org/10.1155/2015/105828. (PMID: 10.1155/2015/105828266932054674598)
Vyas S, Rodrigues AJ, Silva JM, Tronche F, Almeida OF, Sousa N, Sotiropoulos I (2016) Chronic Stress and Glucocorticoids: From Neuronal Plasticity to Neurodegeneration. Neural Plast 2016:6391686. https://doi.org/10.1155/2016/6391686. (PMID: 10.1155/2016/6391686270348474806285)
Wang WY, Tan MS, Yu JT, Tan L (2015) Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Annals of Translational Medicine 3:136. https://doi.org/10.3978/j.issn.2305-5839.2015.03.49. (PMID: 10.3978/j.issn.2305-5839.2015.03.49262072294486922)
Waragai M, Ho G, Takamatsu Y, Wada R, Sugama S, Takenouchi T, Masliah E, Hashimoto M (2020) Adiponectin Paradox in Alzheimer’s Disease; Relevance to Amyloidogenic Evolvability? Front Endocrinol 11:108. https://doi.org/10.3389/fendo.2020.00108. (PMID: 10.3389/fendo.2020.00108)
Zeng Y, Han X (2008) Sulfatides facilitate apolipoprotein E-mediated amyloid-beta peptide clearance through an endocytotic pathway. J Neurochem 106:1275–1286. https://doi.org/10.1111/j.1471-4159.2008.05481.x. (PMID: 10.1111/j.1471-4159.2008.05481.x184851012574953)
Zhu Z, Yan J, Jiang W, Yao XG, Chen J, Chen L, Li C, Hu L, Jiang H, Shen X (2013) Arctigenin effectively ameliorates memory impairment in Alzheimer’s disease model mice targeting both β-amyloid production and clearance. J Neurosci 33:13138–13149. https://doi.org/10.1523/JNEUROSCI.4790-12.2013. (PMID: 10.1523/JNEUROSCI.4790-12.2013239262676619735)

Keywords: Adiponectin; Alzheimer’s disease; Multiple signaling Pathway; Obesity

0 (Adiponectin)
0 (Insulin)
0 (Leptin)

Date Created: 20210528 Date Completed: 20220331 Latest Revision: 20220331

20240829

10.1007/s11011-021-00756-x

34047927