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• W2128743493 abstract "Levels of the obese gene product leptin are often elevated in obesity and may contribute to obesity‐induced cardiovascular complications. However, the role of leptin in obesity‐associated cardiac abnormalities has not been clearly defined. This study was designed to determine the influence of high‐fat diet‐induced obesity on cardiac contractile response of leptin. Mechanical and intracellular Ca 2+ properties were evaluated using an IonOptix system in cardiomyocytes from adult rats fed low‐ and high‐fat diets for 12 weeks. Cardiomyocyte contractile and intracellular Ca 2+ properties were examined including peak shortening, duration and maximal velocity of shortening/relengthening (TPS/TR 90 , ±dl/dt), Fura‐2‐fluorescence intensity change (ΔFFI), and intracellular Ca 2+ decay rate (τ). Expression of the leptin receptor (Ob‐R) was evaluated by western blot analysis. High‐fat diet increased systolic blood pressure and plasma leptin levels. PS and ±dl/dt were depressed whereas TPS and TR 90 were prolonged after high‐fat diet feeding. Leptin elicited a concentration‐dependent (0–1,000 nmol/l) inhibition of PS, ±dl/dt, and ΔFFI in low‐fat but not high‐fat diet‐fed rat cardiomyocytes without affecting TPS and TR 90 . The Janus kinase 2 (JAK2) inhibitor AG490, the mitogen‐activated protein kinase (MAPK) inhibitor SB203580, and the nitric oxide synthase (NOS) inhibitor L‐NAME abrogated leptin‐induced cardiomyocyte contractile response in low‐fat diet group without affecting the high‐fat diet group. High‐fat diet significantly downregulated cardiac expression of Ob‐R. Elevation of extracellular Ca 2+ concentration nullified obesity‐induced cardiomyocyte mechanical dysfunction and leptin‐induced depression in PS. These data indicate presence of cardiac leptin resistance in diet‐induced obesity possibly associated with impaired leptin receptor signaling." @default.
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• W2128743493 date "2008-11-01" @default.
• W2128743493 modified "2023-10-17" @default.
• W2128743493 title "High-fat Diet-induced Obesity Leads to Resistance to Leptin-induced Cardiomyocyte Contractile Response" @default.
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• W2128743493 doi "https://doi.org/10.1038/oby.2008.381" @default.
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