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

Proceedings of the National Academy of Sciences of the United States of America
Shubha V Y RajuJoshua M Hare

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/...Continue Reading

References

Aug 1, 1994·Cardiovascular Drugs and Therapy·E Kaplinsky
Feb 1, 1996·The New England Journal of Medicine·R V ConsidineT L Bauer
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·I GloaguenR Laufer
Sep 1, 1997·The Journal of Clinical Endocrinology and Metabolism·G A Bray, D A York
Oct 10, 1997·Hypertension·W G HaynesA L Mark
Apr 15, 2000·Nature·M W SchwartzD G Baskin
May 17, 2000·Pharmaceutica acta Helvetiae·M W SleemanS J Wiegand
Mar 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·P D LambertS J Wiegand
Jan 16, 2002·Physiology & Behavior·P J Scarpace, N Tümer
May 22, 2002·Cellular Signalling·Gary Sweeney
Aug 2, 2003·Circulation Research·Venkatesh RajapurohitamMorris Karmazyn
Nov 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·M W SleemanS J Wiegand
Dec 18, 2003·Clinical Endocrinology·Nicholas A TritosPeter G Danias
Nov 13, 2004·Circulation Research·Faisal SyedGerald W Dorn

❮ Previous
Next ❯

Citations

May 29, 2007·Basic Research in Cardiology·P Fischer, D Hilfiker-Kleiner
Oct 6, 2007·Basic Research in Cardiology·Philipp Fischer, Denise Hilfiker-Kleiner
Oct 31, 2008·Current Hypertension Reports·Jun Ren, Heng Ma
Dec 15, 2006·Cardiovascular Research·Naveen SharmaWilliam C Stanley
Jun 8, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Vladimir E Bondarenko, Randall L Rasmusson
Feb 23, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Mohammad Nurulqadr JameelJianyi Zhang
Apr 9, 2008·Physiological Reviews·E Dale AbelGary Sweeney
Jul 11, 2008·The Journal of Comparative Neurology·Richa B Tripathi, Dana M McTigue
Aug 22, 2014·Obesity·Timon SeegerStefanie Dimmeler
Jul 21, 2015·Cytokine & Growth Factor Reviews·Miguel López-YoldiMatilde Bustos
Jun 13, 2015·International Journal of Endocrinology·C M GhantousA Zeidan
Nov 17, 2007·Cardiovascular Research·Kenneth R McGaffinChristopher P O'Donnell
Sep 9, 2017·International Journal of Obesity : Journal of the International Association for the Study of Obesity·N Di LascioF Faita
Aug 19, 2007·Circulation Research·Gary D LopaschukWilliam C Stanley
Sep 18, 2007·Circulation Research·Ronghua Yang, Lili A Barouch
Apr 12, 2008·Current Opinion in Clinical Nutrition and Metabolic Care·Galia Gat-Yablonski, Moshe Phillip
Nov 24, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Patrick YuePhilip S Tsao
Mar 14, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Susan A MarshJohn C Chatham
Jan 30, 2018·Diabetes, Obesity & Metabolism·Angelo Avogaro, Gian Paolo Fadini
Feb 16, 2021·Biochemical and Biophysical Research Communications·Peng ZhongJianye Peng
Oct 18, 2007·Current Opinion in Endocrinology, Diabetes, and Obesity

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Cardiomegaly

Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.