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Interaction between age and obesity on cardiomyocyte contractile function: role of leptin and stress signaling
- Source :
- PLoS ONE, Vol 5, Iss 4, p e10085 (2010), PLoS ONE
- Publication Year :
- 2009
-
Abstract
- OBJECTIVES This study was designed to evaluate the interaction between aging and obesity on cardiac contractile and intracellular Ca2+ properties. METHODS 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 (TR(90)), intracellular Ca2+ levels and decay. O2(-) levels were measured by dihydroethidium fluorescence. RESULTS Our results revealed reduced survival in ob/ob mice. Aging and obesity reduced PS, +/- dL/dt, intracellular Ca2+ rise, prolonged TR(90) and intracellular Ca2+ decay, enhanced O2(-) production and p(47phox) 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 pIkappaB. Low levels of leptin reconciled contractile, intracellular Ca2+ and cell signaling defects as well as O2(-) production and p(47phox) 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. CONCLUSIONS 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.
- Subjects :
- Leptin
Male
medicine.medical_specialty
Aging
Nitric Oxide Synthase Type III
lcsh:Medicine
Mice, Obese
030204 cardiovascular system & hematology
Diabetes and Endocrinology/Obesity
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
Enos
Stress, Physiological
Superoxides
Internal medicine
medicine
Animals
Myocytes, Cardiac
Calcium Signaling
Obesity
lcsh:Science
Protein kinase B
Cells, Cultured
030304 developmental biology
2. Zero hunger
0303 health sciences
Multidisciplinary
Leptin receptor
biology
lcsh:R
biology.organism_classification
Dietary Fats
Myocardial Contraction
Geriatrics/Geriatric Cardiology
Endocrinology
Phosphorylation
Cardiovascular Disorders/Myopathies
lcsh:Q
Signal transduction
Proto-Oncogene Proteins c-akt
Intracellular
Research Article
Signal Transduction
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 5
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....fb6962cca69f66e97e40f75f7185ca44