title: Leptin attenuates cerebral ischemia injury through the promotion of energy metabolism via the PI3K/Akt pathway.
abstract: The purpose of this study was to investigate the protective mechanism of leptin-mediated metabolic recovery against cerebral injury after ischemia and reperfusion. We determined the neurologic deficit score, extent of brain edema, and infarct volume after reperfusion. The histopathologic alterations and changes in glucose uptake in the brain were also observed. Moreover, the levels of lactate dehydrogenase (LDH), lactic acid, pyruvate, and ATP in brain tissue were detected. Leptin levels in serum were also detected. To further define leptin-induced neuroprotective signaling pathways, we examined the levels of phosphorylated Akt (p-Akt) in the brain and in cultured cells. After transient ischemia, leptin treatment markedly reduced the neurologic deficits, cerebral infarct volume, and brain edema. After leptin injection, ATP, leptin, and p-Akt levels were significantly increased, LDH levels and lactic acid/pyruvate ratio were noticeably reduced, and histopathologic injuries were alleviated, which were all reversed by the PI(3)K inhibitor LY294002. These data show that leptin ameliorates cerebral ischemia/reperfusion injury by enhancing p-Akt, which in turn improves the supply of energy. The PI(3)K/Akt pathway was found to be the critical pathway for the mediation of leptin-induced neuroprotection, a finding that may prove to be useful in the treatment of ischemic stroke.
authors.affiliation: Research Laboratory of Biochemistry, Basic Medical Institute, General Hospital of the Chinese People's Liberation Army and Military Medical Postgraduate College, Beijing, PR China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhang
authors.forename: Zihui
authors.initials: Z
authors.lastname: Deng
authors.forename: Jie
authors.initials: J
authors.lastname: Liao
authors.forename: Cuihong
authors.initials: C
authors.lastname: Song
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.forename: Luhuan
authors.initials: L
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Guangtao
authors.initials: G
authors.lastname: Yan
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002867:Chromones / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D007770:L-Lactate Dehydrogenase; D019344:Lactic Acid; D020738:Leptin; D009025:Morpholines; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019289:Pyruvic Acid; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one