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Rapid cardiac dysfunction caused by inducible cardiac specific leptin receptor deletion
Author(s) -
Hall Michael Edward,
Hall John E.,
Smith Grant,
Stec David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.743.3
Subject(s) - leptin , medicine , endocrinology , cardiac function curve , leptin receptor , cre recombinase , lipotoxicity , ejection fraction , heart failure , receptor , knockout mouse , genetically modified mouse , biology , transgene , obesity , biochemistry , insulin resistance , gene
Leptin has been hypothesized to play a role in protecting the heart against lipotoxicity in obesity, and disruption of leptin signaling has been associated with cardiac lipid accumulation and dysfunction. However, the importance of leptin's direct effects on cardiac function is unclear. Using the Cre‐loxP recombinase system in C57B/J6 mice, we created an inducible, cardiac‐specific leptin receptor deficient model and assessed cardiac function with serial high resolution echocardiography (EC). Baseline data were obtained on 5 transgenic (TG) mice and 3 age matched (16–18 weeks) controls prior to induction of cardiac leptin receptor knockout with tamoxifen. Baseline ejection fraction (EF) and fractional shortening (FS) were not different between the groups and averaged 69 ± 5 and 39 ± 4% respectively. Seven days after initiation of the knockout, TG mice had a mean EF of 12 ± 1 and FS of 5 ± 0.5%, compared to 68 ± 3 and 38 ± 2%, respectively, in control mice. Heart weight/body weight ratios were higher in TG (7.69 mg/g) compared to control mice (5.45 mg/g). Acute cardiac specific deletion of the leptin receptor results in severe LV systolic dysfunction and rapid heart failure. The mechanism by which this occurs is unclear and could be related to altered cardiac metabolism, mitochondrial dysfunction, or other toxic effects of sudden cardiac leptin receptor deletion in adult mice (PO1 HL51971).