References
Query Results -- Details
MGI Accession ID: MGI:3611416
J Number: J:104171
Other Accession IDs:
Title: Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice.
Authors: Dong F; Zhang X; Yang X; Esberg LB; Yang H; Zhang Z; Culver B; Ren J
Journal: J Endocrinol
Volume: 188
Issue: 1
Date: 2006 Jan
Year: 2006
Pages: 25-36
Review Status: Peer Reviewed
Abstract:
The level of the obese gene product leptin is often positively correlated with body weight, supporting the notion that hyperleptinemia contributes to obesity-associated cardiac dysfunction. However, a link between leptin levels and cardiac function has not been elucidated. This study was designed to examine the role of leptin deficiency (resulting from a point mutation of the leptin gene) in cardiomyocyte contractile function. Mechanical properties and intracellular Ca(2 +) transients were evaluated in ventricular myocytes from lean control and leptin-deficient ob/ob obese mice at 12 weeks of age. Cardiac ultrastructure was evaluated using transmission electron microscopy. ob/ob mice were overtly obese, hyperinsulinemic, hypertriglycemic, hypoleptinemic and euglycemic. Ultrastructural examination revealed swelling and disorganization of cristae in mitochondria from ob/ob mouse ventricular tissues. Cardiomyocytes from ob/ob mice displayed reduced expression of the leptin receptor Ob-R, larger cross-sectional area, decreased peak shortening and maximal velocity of shortening/relengthening, and prolonged relengthening but not shortening duration compared with lean counterparts. Consistent with mechanical characteristics, myocytes from ob/ob mice displayed reduced intracellular Ca(2 +) release upon electrical stimulus associated with a slowed intracellular Ca(2 +) decay rate. Interestingly, the contractile aberrations seen in ob/ob myocytes were significantly improved by in vitro leptin incubation. Contractile dysfunction was not seen in age- and gender-matched high fat-induced obese mice. These results suggested that leptin deficiency contributes to cardiac contractile dysfunction characterized by both systolic and diastolic dysfunction, impaired intracellular Ca(2 +) hemostasis and ultrastructural derangement in ventricular myocytes.
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