NDLI: Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptin-resistant obesity

Content Provider	PubMed Central
Author	Raju, Shubha V. Y. Zheng, Meizi Schuleri, Karl H. Phan, Alexander C. Bedja, Djahida Saraiva, Roberto M. Omer, Yiginer Vandegaer, Koenraad Gabrielson, Kathleen L. O’donnell, Christopher P. Berkowitz, Dan E. Barouch, Lili A. Hare, Joshua M.
Copyright Year	2006
Abstract	Disruption of the leptin signaling pathway within the heart causes left ventricular hypertrophy (LVH). Because human obesity is a syndrome of leptin resistance, which is not amenable to leptin treatment, the identification of parallel signal transduction pathways is of potential therapeutic value. Ciliary neurotrophic factor (CNTF), which acts parallel to leptin in the hypothalamus, is not previously recognized to have cardiac activity. We hypothesized that CNTF receptors are present on cardiomyocytes and their activation reverses LVH in both leptin-deficient ob/ob and leptin-resistant db/db mice. The localization of CNTF receptors (CNTFRα) to the sarcolemma in C57BL/6, ob/ob and db/db was confirmed in situ with immunohistochemistry, and immunoblotting (60 and 40 kDa) on isolated myocytes. ob/ob mice were randomly assigned to receive s.c. recombinant CNTF (CNTFAx15; 0.1 mg·kg−1 per day; n = 11) calorie-restriction (n = 9), or feeding ad libitum (n = 11). db/db mice were allocated to three similar groups (n = 8, 7, and 8, respectively) plus a leptin group (1 mg·kg−1 per day; n = 7). Echocardiography showed that CNTFAx15 reduced cardiac hypertrophy [posterior wall thickness decreased by 29 ± 8% (P < 0.01) in ob/ob and by 21 ± 3% in db/db mice (P < 0.01)], which was consistent with the reduction of myocyte width. Western blotting showed that leptin and CNTFAx15 activated Stat3 and ERK1/2 pathway in cultured adult mice cardiomyocytes and cardiac tissue from in ob/ob and db/db mice. Together, these findings support the role of a previously undescribed signaling pathway in obesity-associated cardiac hypertrophy and have therapeutic implications for patients with obesity-related cardiovascular disease and other causes of LVH.
Related Links	http://dx.doi.org/10.1073/pnas.0510460103
Ending Page	4227
Page Count	6
Starting Page	4222
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	103
Language	English
Publisher	National Academy of Sciences
Publisher Date	2006-03-14
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptin-resistant obesity.

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