title: Long-lasting partnership between insulin resistance and endothelial dysfunction: role of metabolic memory.
abstract: OBJECTIVE
  The persistence of deleterious effects of hyperglycaemia even after glucose normalization is referred to as 'metabolic memory'. However, similar persistent effects of the metabolic consequences of a high fat diet (HFD) have not been described.
  
  
  METHODS
  Rats were given a normal pellet diet (NPD) or a HFD for 3 months. The animals from the HFD group were then returned to the NPD to observe the long-term effects of insulin resistance. Endothelial dysfunction was assessed by carbachol-mediated vasorelaxation and eNOS phosphorylation.
  
  
  RESULTS
  As expected, HFD consumption resulted in insulin resistance and endothelial dysfunction. Phosphorylation of eNOS at S1177 was decreased in HFD rats, compared with that in the NPD group. Rats on 3 months of HFD showed glucose intolerance and impaired insulin sensitivity and were then switched back to NPD (REV group) . Levels of cholesterol and triglyceride, and adiposity returned to normal in REV rats. However, endothelium-dependent vascular responses to carbachol which were impaired in HFD rats, continued to be impaired in REV rats. Similarly, decreased eNOS phosphorylation after HFD was not improved after 1 or 6 months of REV.
  
  
  CONCLUSIONS
  Our data indicate that returning to NPD did not improve the insulin sensitivity or the endothelial dysfunction induced by HFD. Although some biochemical parameters responsible for insulin resistance and endothelial dysfunction were normalized, molecular and vascular abnormalities, involving NO, persisted for several months, highlighting the long-lasting effects of metabolic memory.
authors.affiliation: Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Mohali, Punjab, India.
authors.forename: Divya Sri Priyanka
authors.initials: DS
authors.lastname: Tallapragada
authors.affiliation: Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Mohali, Punjab, India.
authors.forename: Pinakin Arun
authors.initials: PA
authors.lastname: Karpe
authors.affiliation: Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Mohali, Punjab, India.
authors.forename: Kulbhushan
authors.initials: K
authors.lastname: Tikoo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002217:Carbachol / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014665:Vasodilator Agents; D002217:Carbachol
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