title: Absence of fatty acid transporter CD36 protects against Western-type diet-related cardiac dysfunction following pressure overload in mice.
abstract: Cardiac patients often are obese and have hypertension, but in most studies these conditions are investigated separately. Here, we aimed at 1) elucidating the interaction of metabolic and mechanophysical stress in the development of cardiac dysfunction in mice and 2) preventing this interaction by ablation of the fatty acid transporter CD36. Male wild-type (WT) C57Bl/6 mice and CD36(-/-) mice received chow or Western-type diet (WTD) for 10 wk and then underwent a sham surgery or transverse aortic constriction (TAC) under anesthesia. After a 6-wk continuation of the diet, cardiac function, morphology, lipid profiles, and molecular parameters were assessed. WTD administration affected body and organ weights of WT and CD36(-/-) mice, but it affected only plasma glucose and insulin concentrations in WT mice. Cardiac lipid concentrations increased in WT mice receiving WTD, decreased in CD36(-/-) on chow, and remained unchanged in CD36(-/-) receiving WTD. TAC induced cardiac hypertrophy in WT mice on chow but did not affect cardiac function and cardiac lipid concentrations. WTD or CD36 ablation worsened the outcome of TAC. Ablation of CD36 protected against the WTD-related aggravation of cardiac functional and structural changes induced by TAC. In conclusion, cardiac dysfunction and remodeling worsen when the heart is exposed to two stresses, metabolic and mechanophysical, at the same time. CD36 ablation prevents the metabolic stress resulting from a WTD. Thus, metabolic conditions are a critical factor for the compromised heart and provide new targets for metabolic manipulation in cardioprotection.
authors.affiliation: Cardiovascular Research Institute Maastricht, Department of Molecular Genetics, Maastricht University Medical Center+, The Netherlands. laura.steinbusch@maastrichtuniversity.nl
authors.forename: Laura K M
authors.initials: LK
authors.lastname: Steinbusch
authors.forename: Joost J F P
authors.initials: JJ
authors.lastname: Luiken
authors.forename: Ronald
authors.initials: R
authors.lastname: Vlasblom
authors.forename: Adrian
authors.initials: A
authors.lastname: Chabowski
authors.forename: Nicole T H
authors.initials: NT
authors.lastname: Hoebers
authors.forename: Will A
authors.initials: WA
authors.lastname: Coumans
authors.forename: Irene O C M
authors.initials: IO
authors.lastname: Vroegrijk
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.forename: D Margriet
authors.initials: DM
authors.lastname: Ouwens
authors.forename: Jan F C
authors.initials: JF
authors.lastname: Glatz
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000150:complications; D001786:Blood Glucose / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D004032:Diet; D006321:Heart / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000150:complications
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens