ArticleProceedings of the National Academy of Sciences of the United States of America2006
Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptin-resistant obesity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 50 citations in OpenAlex.
- Ciliary neurotrophic factor attenuates myocardial infarction-induced oxidative stress and ferroptosis via PI3K/Akt signaling.Journal of molecular histology · 2025Article
- AAV9-Mediated Cardiac CNTF Overexpression Exacerbated Adverse Cardiac Remodeling in Streptozotocin-Induced Type 1 Diabetic Models.Cardiovascular toxicology · 2022Article
- Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience.Cell metabolism · 2021Review
- Effects of Caloric Restriction Diet on Arterial Hypertension and Endothelial Dysfunction.Nutrients · 2021Review
- Leptin as a Key between Obesity and Cardiovascular Disease.Journal of obesity & metabolic syndrome · 2020Review
- Caloric restriction reverses left ventricular hypertrophy through the regulation of cardiac iron homeostasis in impaired leptin signaling mice.Scientific reports · 2020Article
- Effects of Cardiovascular Risk Factors on Cardiac STAT3.International journal of molecular sciences · 2018Review
- Longitudinal micro-ultrasound assessment of the ob/ob mouse model: evaluation of cardiovascular, renal and hepatic parameters.International journal of obesity (2005) · 2018Article
- Quantitative trait loci with sex-specific effects for internal organs weights and hematocrit value in a broiler-layer cross.Journal of applied genetics · 2016Article
- Differential Role of Leptin and Adiponectin in Cardiovascular System.International journal of endocrinology · 2015Review
- Corneal endothelial autocrine VIP enhances its integrity in stored human donor corneoscleral explant.Investigative ophthalmology & visual science · 2011Article
- Transmural heterogeneity of repolarization and Ca2+ handling in a model of mouse ventricular tissue.American journal of physiology. Heart and circulatory physiology · 2010Article
- Long-term functional improvement and gene expression changes after bone marrow-derived multipotent progenitor cell transplantation in myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2010Article
- CNTF-evoked activation of JAK and ERK mediates the functional expression of T-type Ca2+ channels in chicken nodose neurons.Journal of neurochemistry · 2009Article
- Impaired cardiac function in leptin-deficient mice.Current hypertension reports · 2008Review
- Chronically increased ciliary neurotrophic factor and fibroblast growth factor-2 expression after spinal contusion in rats.The Journal of comparative neurology · 2008Article
- Influence of maternal undernutrition and overfeeding on cardiac ciliary neurotrophic factor receptor and ventricular size in fetal sheep.The Journal of nutritional biochemistry · 2008Article
- Cardiac remodeling in obesity.Physiological reviews · 2008Review
- Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy.Cardiovascular research · 2007Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
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 (CNTFRalpha) 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 (CNTF(Ax15); 0.1 mg x 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 x kg(-1) per day; n = 7). Echocardiography showed that CNTF(Ax15) 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 CNTF(Ax15) 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.
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