title: Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet.
abstract: BACKGROUND
  It remains to be established if, and to what extent, the coronary microcirculation becomes compromised during the development of obesity and insulin resistance. Recent studies suggest that changes in endothelial glycocalyx properties contribute to microvascular dysfunction under (pre-)diabetic conditions. Accordingly, early effects of diet-induced obesity on myocardial perfusion and function were studied in rats under baseline and hyperaemic conditions.
  
  
  METHODS
  Rats were fed a high fat diet (HFD) for 6 weeks and myocardial microvascular perfusion was determined using first-pass perfusion MRI before and after adenosine infusion. The effect of HFD on microcirculatory properties was also assessed by sidestream darkfield (SDF) imaging of the gastrocnemius muscle.
  
  
  RESULTS
  HFD-fed rats developed central obesity and insulin sensitivity was reduced as evidenced by the marked reduction in insulin-induced phosphorylation of Akt in both cardiac and gastrocnemius muscle. Early diet-induced obesity did not lead to hypertension or cardiac hypertrophic remodeling. In chow-fed, control rats a robust increase in cardiac microvascular perfusion was observed upon adenosine infusion (+40%; p < 0.05). In contrast, the adenosine response was abrogated in rats on a HFD (+8%; N.S.). HFD neither resulted in rarefaction or loss of glycocalyx integrity in skeletal muscle, nor reduced staining intensity of the glycocalyx of cardiac capillaries.
  
  
  CONCLUSIONS
  Alterations in coronary microcirculatory function as assessed by first-pass perfusion MRI represent one of the earliest obesity-related cardiac adaptations that can be assessed non-invasively. In this early stage of insulin resistance, disturbances in glycocalyx barrier properties appeared not to contribute to the observed changes in coronary microvascular function.
authors.affiliation: Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. j.vanhaare@maastrichtuniversity.nl.
authors.forename: Judith
authors.initials: J
authors.lastname: van Haare
authors.affiliation: Department of Radiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. eline.kooi@mumc.nl.
authors.forename: M Eline
authors.initials: ME
authors.lastname: Kooi
authors.affiliation: Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. h.vink@maastrichtuniversity.nl.
authors.forename: Hans
authors.initials: H
authors.lastname: Vink
authors.affiliation: Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. m.post@maastrichtuniversity.nl.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Post
authors.affiliation: Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. j.vanteeffelen@maastrichtuniversity.nl.
authors.forename: Jurgen W G E
authors.initials: JW
authors.lastname: van Teeffelen
authors.affiliation: Department of Radiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. j.slenter@maastrichtuniversity.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: Slenter
authors.affiliation: Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. c.munts@maastrichtuniversity.nl.
authors.forename: Chantal
authors.initials: C
authors.lastname: Munts
authors.affiliation: Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. hanneke.cobelens@maastrichtuniversity.nl.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Cobelens
authors.affiliation: Biomedical Engineering and Physics, Academic Medical Center, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands. g.j.strijkers@amc.uva.nl.
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.affiliation: Pie Medical Imaging, P.O. Box 1132, 6201 BC, Maastricht, The Netherlands. dennis.koehn@pie.nl.
authors.forename: Dennis
authors.initials: D
authors.lastname: Koehn
authors.affiliation: Department of Physiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. marc.vanbilsen@maastrichtuniversity.nl.|Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. marc.vanbilsen@maastrichtuniversity.nl.
authors.forename: Marc
authors.initials: M
authors.lastname: van Bilsen
mesh_terms: D000241:Adenosine / Q000008:administration & dosage; D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D019276:Glycocalyx / Q000378:metabolism; D006940:Hyperemia / Q000503:physiopathology; D007333:Insulin Resistance; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008833:Microcirculation; D055806:Microvessels / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D055414:Myocardial Perfusion Imaging / Q000379:methods; D009206:Myocardium / Q000378:metabolism; D056128:Obesity, Abdominal / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D011236:Prediabetic State / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage; D020257:Ventricular Remodeling
chemical_list: D014665:Vasodilator Agents; D051057:Proto-Oncogene Proteins c-akt; D000241:Adenosine