title: Modification of high saturated fat diet with n-3 polyunsaturated fat improves glucose intolerance and vascular dysfunction.
abstract: OBJECTIVE
  The ability of dietary enrichment with monounsaturated fatty acid (MUFA), n-3 or n-6 polyunsaturated fatty acids (PUFAs) to reverse glucose intolerance and vascular dysfunction resulting from excessive dietary saturated fatty acids is not resolved. We hypothesized that partial replacement of dietary saturated fats with n-3 PUFA-enriched menhaden oil (MO) would provide greater improvement in glucose tolerance and vascular function compared to n-6 enriched safflower oil (SO) or MUFA-enriched olive oil (OO).
  
  
  METHODS
  We fed mice a high saturated fat diet (HF) (60% kcal from lard) for 12 weeks before substituting half the lard with MO, SO or OO for an additional 4 weeks. At the end of 4 weeks, we assessed glucose tolerance, insulin signalling and reactivity of isolated pressurized gracilis arteries.
  
  
  RESULTS
  After 12 weeks of saturated fat diet, body weights were elevated and glucose tolerance was abnormal compared to mice on control diet (13% kcal lard). Diet substituted with MO restored basal glucose levels, glucose tolerance and indices of insulin signalling (phosphorylated Akt) to normal, whereas restoration was limited for SO and OO substitutions. Although dilation to acetylcholine was reduced in arteries from mice on HF, OO and SO diets compared to normal diet, dilation to acetylcholine was fully restored and constriction to phenylephrine was reduced in MO-fed mice compared to normal.
  
  
  CONCLUSIONS
  We conclude that short-term enrichment of an ongoing high fat diet with n-3 PUFA rich MO, but not MUFA rich OO or n-6 PUFA rich SO, reverses glucose tolerance, insulin signalling and vascular dysfunction.
authors.affiliation: Iowa City Veterans Affairs Health Care System, Iowa City, IA 52246, USA. kathryn-lamping@uiowa.edu
authors.forename: K G
authors.initials: KG
authors.lastname: Lamping
authors.forename: D W
authors.initials: DW
authors.lastname: Nuno
authors.forename: L J
authors.initials: LJ
authors.lastname: Coppey
authors.forename: A J
authors.initials: AJ
authors.lastname: Holmes
authors.forename: S
authors.initials: S
authors.lastname: Hu
authors.forename: C L
authors.initials: CL
authors.lastname: Oltman
authors.forename: A W
authors.initials: AW
authors.lastname: Norris
authors.forename: M A
authors.initials: MA
authors.lastname: Yorek
mesh_terms: D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat; D004041:Dietary Fats; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D002149:Energy Intake; D005227:Fatty Acids / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D018149:Glucose Intolerance; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000069463:Olive Oil; D010938:Plant Oils; D012450:Safflower Oil; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism; D014652:Vascular Diseases / Q000178:diet therapy / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D015525:Fatty Acids, Omega-3; D000069463:Olive Oil; D010938:Plant Oils; D014280:Triglycerides; D012450:Safflower Oil; C029310:lard