title: Effects of high-fat diet on insulin receptor function in rat hippocampus and the level of neuronal corticosterone.
abstract: OBJECTIVE
  Chronic consumption of a high-fat (HF) diet contributes to peripheral insulin resistance and elevated plasma corticosterone. However, the effect of HF consumption on the neurofunctional insulin receptors and neuronal corticosterone level is unclear. We tested the hypothesis that HF consumption can lead to peripheral insulin resistance, elevated neuronal corticosterone, and impaired neuronal responses to insulin.
  
  
  METHODS
  Male Wistar rats were fed with normal diet or HF diet for 4, 8 or 12weeks. At the end of each dietary period, plasma was collected for investigating peripheral insulin resistance parameters and corticosterone. Brains were then rapidly removed for studying the function of neuronal insulin receptors (IRs) by extracellular recording in CA1 hippocampus, neuronal IR signaling by immunoblot technique and neuronal corticosterone.
  
  
  RESULTS
  Elevated plasma corticosterone level was initially seen in 4-week HF-fed rats. Peripheral insulin resistance developed at 8-week HF-fed rats. However, the elevated neuronal corticosterone level was found at 12-week HF consumption. The neuronal IR response demonstrated by insulin-mediated long-term depression in CA1 hippocampus was diminished in 12-week HF-fed rats. The phosphorylation levels of neuronal IR, IR substrate 1 and Akt/PKB were decreased in 12-week HF-fed rats with no change in these proteins. There was a correlation among peripheral insulin resistance, neuronal stress (elevated neuronal corticosterone), and neuronal insulin resistance in HF group.
  
  
  CONCLUSIONS
  Our findings suggest that HF consumption can lead to the elevation of corticosterone and peripheral insulin resistance, which could contribute to neuronal insulin resistance and neuronal stress.
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
authors.forename: Wasana
authors.initials: W
authors.lastname: Pratchayasakul
authors.forename: Sasiwan
authors.initials: S
authors.lastname: Kerdphoo
authors.forename: Petnoi
authors.initials: P
authors.lastname: Petsophonsakul
authors.forename: Anchalee
authors.initials: A
authors.lastname: Pongchaidecha
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects*; D004591:Electrophoresis, Polyacrylamide Gel; D005951:Glucose Tolerance Test; D015151:Immunoblotting; D047468:Immunoprecipitation; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
chemical_list: D004041:Dietary Fats; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D011972:Receptor, Insulin; D003345:Corticosterone