TY - JOUR
T1 - Absence of fatty acid transporter CD36 protects against Western-type diet-related cardiac dysfunction following pressure overload in mice
AU - Steinbusch, Laura K. M.
AU - Luiken, Joost J. F. P.
AU - Vlasblom, Ronald
AU - Chabowski, Adrian
AU - Hoebers, Nicole T. H.
AU - Coumans, Will A.
AU - Vroegrijk, Irene O. C. M.
AU - Voshol, Peter J.
AU - Ouwens, D. Margriet
AU - Glatz, Jan F. C.
AU - Diamant, Michaela
PY - 2011/10
Y1 - 2011/10
N2 - Steinbusch LK, Luiken JJ, Vlasblom R, Chabowski A, Hoebers NT, Coumans WA, Vroegrijk IO, Voshol PJ, Ouwens DM, Glatz JF, Diamant M. Absence of fatty acid transporter CD36 protects against Western-type diet-related cardiac dysfunction following pressure overload in mice. Am J Physiol Endocrinol Metab 301: E618-E627, 2011. First published June 28, 2011; doi:10.1152/ajpendo.00106.2011.-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.
AB - Steinbusch LK, Luiken JJ, Vlasblom R, Chabowski A, Hoebers NT, Coumans WA, Vroegrijk IO, Voshol PJ, Ouwens DM, Glatz JF, Diamant M. Absence of fatty acid transporter CD36 protects against Western-type diet-related cardiac dysfunction following pressure overload in mice. Am J Physiol Endocrinol Metab 301: E618-E627, 2011. First published June 28, 2011; doi:10.1152/ajpendo.00106.2011.-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.
KW - lipids
KW - cardiac hypertrophy
KW - metabolic flexibility
KW - obesity
U2 - 10.1152/ajpendo.00106.2011
DO - 10.1152/ajpendo.00106.2011
M3 - Article
C2 - 21712535
SN - 0193-1849
VL - 301
SP - E618-E627
JO - American Journal of Physiology : Endocrinology and Metabolism
JF - American Journal of Physiology : Endocrinology and Metabolism
IS - 4
ER -