title: Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but not in ovariectomized obese rats.
abstract: OBJECTIVE
  We previously demonstrated that obesity caused the reduction of peripheral and brain insulin sensitivity and that estrogen therapy improved these defects. However, the beneficial effect of estrogen on brain insulin sensitivity and oxidative stress in either ovariectomy alone or ovariectomy with obesity models has not been determined. We hypothesized that ovariectomy alone or ovariectomy with obesity reduces brain insulin sensitivity and increases brain oxidative stress, which are reversed by estrogen treatment.
  
  
  METHODS
  Thirty female rats were assigned as either sham-operated or ovariectomized. After the surgery, each group was fed either a normal diet or high-fat diet for 12 weeks. At week 13, rats in each group received either the vehicle or estradiol for 30 days. At week 16, blood and brain were collected for determining the peripheral and brain insulin sensitivity as well as brain oxidative stress.
  
  
  RESULTS
  We found that ovariectomized rats and high-fat diet fed rats incurred obesity, reduced peripheral and brain insulin sensitivity, and increased brain oxidative stress. Estrogen ameliorated peripheral insulin sensitivity in these rats. However, the beneficial effect of estrogen on brain insulin sensitivity and brain oxidative stress was observed only in ovariectomized normal diet-fed rats, but not in ovariectomized high fat diet-fed rats.
  
  
  CONCLUSIONS
  Our results suggested that reduced brain insulin sensitivity and increased brain oxidative stress occurred after either ovariectomy or obesity. However, the reduced brain insulin sensitivity and the increased brain oxidative stress in ovariectomy with obesity could not be ameliorated by estrogen treatment.
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Wasana
authors.initials: W
authors.lastname: Pratchayasakul
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
authors.affiliation: Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Oral Biology and Diagnostic Science, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand. Electronic address: s.chat@chiangmai.ac.th.
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D059305:Diet, High-Fat / Q000009:adverse effects*; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008315:Malondialdehyde / Q000032:analysis; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D010052:Ovariectomy / Q000009:adverse effects*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D004967:Estrogens; D007328:Insulin; D004958:Estradiol; D008315:Malondialdehyde
keywords: Brain insulin signaling; High-fat diet; Insulin-induced LTD; Ovariectomy