title: Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice.
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.
authors.affiliation: Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, 82071, USA.
authors.forename: F
authors.initials: F
authors.lastname: Dong
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.forename: L B
authors.initials: LB
authors.lastname: Esberg
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Culver
authors.forename: J
authors.initials: J
authors.lastname: Ren
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D006352:Heart Ventricles; D020738:Leptin / Q000172:deficiency*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D009765:Obesity / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013481:Superoxides / Q000032:analysis / Q000378:metabolism
chemical_list: D020738:Leptin; D013481:Superoxides; D002118:Calcium