Insulin Resistance as a Risk Factor in Visceral and Neurological Disorders Insulin Resistance as a Risk Factor in Visceral and Neurological Disorders AKHLAQ A. FAROOQUI Department of Molecular and CellularBiochemistry, The Ohio State University, Columbus, OH, UnitedStates AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UnitedKingdom 525BStreet,Suite1650,SanDiego,CA92101,UnitedStates 50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom Copyright©2020ElsevierInc.Allrightsreserved. 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BritishLibraryCataloguing-in-PublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary LibraryofCongressCataloging-in-PublicationData AcatalogrecordforthisbookisavailablefromtheLibraryofCongress ISBN:978-0-12-819603-8 ForInformationonallAcademicPresspublications visitourwebsiteathttps://www.elsevier.com/books-and-journals Publisher:NikkiLevy AcquisitionsEditor:MelanieTucker EditorialProjectManager:KristiAnderson ProductionProjectManager:SujathaThirugnanaSambandam CoverDesigner:MilesHitchen TypesetbyMPSLimited,Chennai,India Dedication This monograph is dedicated to my beloved father “late Sharafyab Ahmed Sahab” whose guidance and influence continue to inspire and support me. Akhlaq A. Farooqui Contents Abouttheauthor xi Preface xiii Acknowledgments xvii Listofabbreviations xix 1. Insulin resistance and obesity 1 Introduction 1 Insulinsignalinginthebrain 3 Insulinresistance 6 Insulinresistanceasaprotectivemechanism 21 Effectsofdietonmicrobiotapopulation 30 Microbiotaandshortchainfattyacids 34 Effectsofgutmicrobiotaandobesityonthebrain 38 Linkamonginsulinsignaling,obesity,andinsulinresistance 42 Contributionofleptininthedevelopmentofobesity 43 Contributionofadiponectininobesity 45 Insulinsignalingobesityandneurologicaldisorders 47 Conclusion 49 References 50 Furtherreading 69 2. Insulin resistance, diabetes, andmetabolic syndrome 71 Introduction 71 Biomarkersfortype2diabetes 77 miRNAs,diabetes,andvascularcomplications 78 Comlicationscausedbytype2diabetes 79 Molecularmechanismscontributingtotype2diabetescomplications 83 Riskfactorscontributingtometabolicsyndrome 88 Pathogenesisofmetabolicsyndrome 89 Linkbetweentype2diabetesandmetabolicsyndrome 92 Type2diabetesandmetabolicsyndromeasriskfactorsforAlzheimer’s disease 94 Conclusion 100 References 101 Furtherreading 111 vii viii Contents 3. Insulin resistance and heart disease 113 Introduction 113 Insulinsignalinginvasculature 121 Molecularmechanismofatherosclerosis 133 Carbohydratemetabolism,insulinresistance,andheartdisease 136 Biochemicallinksbetweeninsulinresistanceandheartdisease 140 Contributionoflipidmediatorsinheartdisease 140 Conclusion 143 References 144 Furtherreading 155 4. Insulin resistance and sleep apnea 157 Introduction 157 Obstructivesleepapnea 160 Biochemicalchangesinobstructivesleepapnea 162 Oxidativestress,insulinresistance,andobstructivesleepapnea 162 Obstructivesleepapnea(cid:1)mediatedchangesinlipidmetabolism 167 Inflammation,insulinresistance,andobstructivesleepapnea 168 Biomarkersforobstructivesleepapnea 170 Obstructivesleepapneaandheartdisease 172 Obstructivesleepapneaandhypertension 175 Obstructivesleepapneaandmetabolicsyndrome 176 Obstructivesleepapneaandstroke 179 Obstructivesleepapneaanditsrelationshipwithvariousdiseases 182 ObstructivesleepapneaandAlzheimer’sdisease 184 Obstructivesleepapneaanddepression 189 Conclusion 191 References 191 Furtherreading 205 5. Insulin resistance and stroke 207 Introduction 207 Hypertensionandpathogenesisofstroke 212 Contributionofdiet,microbiota,andinsulinresistanceinthepathogenesis ofstroke 215 Stroke-mediatedchangesinthebrain 218 Molecularlinkamongadvancedglycatedendproducts,insulinresistance, andstroke 230 Adipokines,insulinresistance,andstroke 233 Contents ix Molecularlinkbetweenhypertensionandbraindamage 234 Effectofmicrobiotacompositiononstrokeoutcome 236 Conclusion 238 References 239 Furtherreading 248 6. Insulin resistance and Alzheimer’sdisease 249 Introduction 249 Insulinsignalinginthebrain 250 PathogenesisofAlzheimer’sdisease 255 Insulinreceptor,insulinsignaling,andinsulinresistanceinthebrain 264 Neurochemicallinksamonginsulinresistance,type2diabetes,and Alzheimer’sdisease 265 Cerebralbloodflowintype2diabetesandAlzheimer’sdisease 271 Ceramode-mediatedinsulinresistanceintype2diabetesandAlzheimer’s disease 273 Conclusion 277 References 278 Furtherreading 291 7. Insulin resistance and Parkinson’sdisease 293 Introduction 293 FamilialParkinson’sdisease 298 SporadicParkinson’sdisease 299 Gutmicrobiota,insulinresistance,andParkinson’sdisease 303 Insulinresistance,type2diabetes,andParkinson’sdisease 308 OverlapbetweenParkinson’sdiseaseandKrabbe’sdisease 316 OverlapbetweenParkinson’sdiseaseandGaucher’sdisease 318 BiomarkersforParkinson’sdisease 319 OxidativestressinParkinson’sdisease 320 NeuroinflammationinParkinson’sdisease 322 DepressionandParkinson’sdisease 324 Conclusion 326 References 327 Furtherreading 342 8. Insulin resistance, dementia, and depression 349 Introduction 349 Normalagingandcognitivefunction 352 x Contents Neurochemicalaspectsofdementia 354 Classificationofdementias 355 Alzheimer’stypeofdementia 356 Neurochemicalaspectsofvasculardementia 359 NeurochemicalaspectsofLewybodydementia 361 Neurochemicalaspectsoffrontotemporaldementia 365 Insulinresistance,stress,anddepression 366 Effectsofdietandexerciseondementiaanddepression 373 Conclusion 374 References 374 Furtherreading 384 9. Use ofphytochemicals for the treatment of insulin resistance(cid:1)linked visceral and neurologicaldisorders 385 Introduction 385 Effectsofvarioustypesofdietsoninsulinresistance 389 Effectsofcurcuminoninsulinresistanceandinsulinresistance(cid:1)linkeddiseases 400 Effectofgreenteaoninsulinresistance(cid:1)linkeddiseases 404 Effectofresveratroloninsulinresistanceandinsulinresistance(cid:1)linkeddiseases 407 Effectofn-3fattyacidsininsulinresistanceandinsulinresistance(cid:1)linked diseases 413 Effectsofcinnamononinsulinresistanceandinsulinresistance(cid:1)linked diseases 415 Effectsofgarliconinsulinresistanceandinsulinresistance(cid:1)linkeddiseases 419 Conclusion 424 References 425 Furtherreading 437 10. Summery and perspective for future research on insulin resistance and insulin resistance(cid:1)linked visceral and neurological disorders 439 Introduction 439 Chronicinsulinresistance:acommonlinkbetweenvisceralandneurological disorders 443 Directionforfutureresearch 453 Conclusion 455 References 456 Index 463 About the author Dr. Akhlaq A. Farooqui is a leader in the field of signal transduction, brain phospholipases A , bioactive ether lipid metabolism, polyunsaturated 2 fatty acid metabolism, glycerophospholipid-, sphingolipid-, and cholesterol-derived lipid mediators, glutamate-induced neurotoxicity, and modulation of signal transduction by phytochemicals. He has discovered the stimulation of plasmalogen-selective phospholipase A (PlsEtn-PLA ) 2 2 and diacyl- and monoacylglycerol lipases in brains from patients with Alzheimer’s disease. Stimulation of PlsEtn-PLA produces plasmalogen 2 deficiency and increases levels of eicosanoids that may be related to the loss of synapses in brains of patients with Alzheimer’s disease. He has pub- lished cutting edge research on the generation and identification of glycer- ophospholipid-, sphingolipid-, and cholesterol-derived lipid mediators in kainic acid(cid:1)mediated neurotoxicity by lipidomics. He has authored 12 monographs: Glycerophospholipids in Brain: Phospholipase A in Neurological 2 Disorders (2007); Neurochemical Aspects of Excitotoxicity (2008); Metabolism and Functions of Bioactive Ether Lipids in Brain (2008); Hot Topics in Neural Membrane Lipidology (2009); Beneficial Effects of Fish Oil in Human Brain (2009); Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases (2010); Lipid Mediators and their Metabolism in the Brain (2011); Phytochemicals, Signal Transduction, and Neurological Disorders (2012); Metabolic Syndrome: An Important Risk Factor for Stroke, Alzheimer’s Disease, and Depression (2013); Inflammation and Oxidative Stress in Neurological Disorders (2014); High Calorie Diet and the Human Brain (2015); and Therapeutic Potentials of Curcumin For Alzheimer’s Disease (2016). All above monographs have been published by Springer, New York and Springer International Publishing Switzerland. Monographs on Neurochemical Aspects of Alzheimer’s Disease (2017), Ischemic, Traumatic Brain, and Spinal Cord Injuries: Mechanisms and Potential Therapies (2018), and Molecular Mechanisms of Dementia: Biomarkers, Neurochemistry, and Therapy have been published by Academic Press: An imprint of Elsevier, San Diego, CA. In addition, he has edited 12 books: Biogenic Amines: Pharmacological, Neurochemical and Molecular Aspects in the CNS (2010), Nova Science Publisher, Hauppauge, New York; Molecular Aspects of Neurodegeneration and Neuroprotection (2011), Bentham Science Publishers Ltd; Phytochemicals and Human Health: Molecular and pharmacological Aspects (2011), Nova xi