Interaction between Age and Obesity on Cardiomyocyte Contractile Function: Role of Leptin and Stress SignalingReportar como inadecuado

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This study was designed to evaluate the interaction between aging and obesity on cardiac contractile and intracellular Ca2+ properties.


Cardiomyocytes from young 4-mo and aging 12- and 18-mo male lean and the leptin deficient ob-ob obese mice were treated with leptin 0.5, 1.0 and 50 nM for 4 hrs in vitro. High fat diet 45% calorie from fat and the leptin receptor mutant db-db obesity models at young and older age were used for comparison. Cardiomyocyte contractile and intracellular Ca2+ properties were evaluated including peak shortening PS, maximal velocity of shortening-relengthening ± dL-dt, time-to-PS TPS, time-to-90% relengthening TR90, intracellular Ca2+ levels and decay. O2− levels were measured by dihydroethidium fluorescence.


Our results revealed reduced survival in ob-ob mice. Aging and obesity reduced PS, ± dL-dt, intracellular Ca2+ rise, prolonged TR90 and intracellular Ca2+ decay, enhanced O2− production and p47phox expression without an additive effect of the two, with the exception of intracellular Ca2+ rise. Western blot analysis exhibited reduced Ob-R expression and STAT-3 phosphorylation in both young and aging ob-ob mice, which was restored by leptin. Aging and obesity reduced phosphorylation of Akt, eNOS and p38 while promoting pJNK and pIκB. Low levels of leptin reconciled contractile, intracellular Ca2+ and cell signaling defects as well as O2− production and p47phox upregulation in young but not aging ob-ob mice. High level of leptin 50 nM compromised contractile and intracellular Ca2+ response as well as O2− production and stress signaling in all groups. High fat diet-induced and db-db obesity displayed somewhat comparable aging-induced mechanical but not leptin response.


Taken together, our data suggest that aging and obesity compromise cardiac contractile function possibly via phosphorylation of Akt, eNOS and stress signaling-associated O2− release.

Autor: Jun Ren , Feng Dong, Guo-Jun Cai, Peng Zhao, Jennifer M. Nunn, Loren E. Wold, Jianming Pei



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