title: Obesity Exacerbates Rat Cerebral Ischemic Injury through Enhancing Ischemic Adiponectin-Containing Neuronal Apoptosis.
abstract: A diet consisting of high levels of saturated fat has been linked to a dramatic rise in obesity. Long-term exposure to high fat, "Western diet" (WD), is detrimental to ischemic brain injury. Adiponectin receptor 1 (ADR-1) activation is also shown to exacerbate ischemic neuronal death. However, it is not known whether increasing percentages of adiponectin (APN)-containing neurons attenuates ischemic neuronal apoptosis by modulating ADRS. To explore the role of APN and its ADRs in the development of acute cerebral injury, we subjected WD and control diet (CD) rats to 1 h of middle cerebral artery occlusion followed by 23 h of reperfusion. Compared with CD rats, WD rats exhibited higher levels of brain infarct, neurologic deficits, brain edema, and apoptosis of APN-containing neurons; upregulation of both ADR-1 and P38 mitogen-activated protein kinase (P38MAPK); and downregulation of ADR-2 in ischemic brain tissues including frontal cortex, striatum, and hippocampus. Increasing percentages of APN-containing neurons by baculovirus-mediated administration of APN, in addition to reducing apoptosis of APN-containing neurons in ischemic brain tissues, significantly attenuated brain infarct and edema, neurologic deficits, and altered expression of ADR-1, P38MAPK, and ADR-2 in both WD and CD group rats. These data suggest a negative correlation between percentages of APN-containing neurons and cerebral ischemic injury. Obesity could exacerbate rat cerebral ischemic injury by enhancing apoptosis of APN-containing neurons in ischemic brain tissues probably via modulating ADRs and P38MAPK.
authors.affiliation: The Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan.|Division of Neurology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Ming-Hsiu
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Chio
authors.affiliation: The Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan.
authors.forename: Kuen-Jer
authors.initials: KJ
authors.lastname: Tsai
authors.affiliation: Department of Biotechnology, Southern University of Science and Technology, Tainan, Taiwan.
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chang
authors.affiliation: Li-Sheng Biotechnology Co., Ltd., Taipei, Taiwan.
authors.forename: Nan-Kai
authors.initials: NK
authors.lastname: Lin
authors.affiliation: The Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan. huangped@mail.ncku.edu.tw.|Department of Pediatrics, Wan-Fan Hospital, College of Medicine, Taipei Medical University, Taipei, Taiwan. huangped@mail.ncku.edu.tw.
authors.forename: Chao-Ching
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan. 891201@mail.chimei.org.tw.
authors.forename: Mao-Tsun
authors.initials: MT
authors.lastname: Lin
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis; D016367:Baculoviridae / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000150:complications / Q000473:pathology; D020520:Brain Infarction / Q000150:complications / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D018450:Disease Progression; D015536:Down-Regulation; D007211:Indoles / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D052242:Adiponectin; D034961:Antigens, Nuclear; D007211:Indoles; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat; D054419:Receptors, Adiponectin; C007293:DAPI; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Adiponectin; Cerebral ischemia; Obesity; P38 mitogen-activated protein kinase; Stroke