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Relationship Between Leptin and Heart Failure: A Meta-Analysis Cover

Relationship Between Leptin and Heart Failure: A Meta-Analysis

By: Xin Sun,  Caihong Xin,  Jiayi Yao and  Hongli Wang  
Open Access
|May 2025

References

  1. 1Savarese G, Becher PM, Lund LH, Seferovic P, Rosano G, Coats A. Global burden of heart failure: A comprehensive and updated review of epidemiology. Cardiovascular Research. 2023;118(17):32723287. DOI: 10.1093/cvr/cvac013
  2. 2American Heart Association. Heart Disease and Stroke Statistics: 2003 Update. Dallas, TX: American Heart Association; 2003.
  3. 3Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, Kannel WB, Vasan RS. Obesity and the risk of heart failure. The New England Journal of Medicine. 2002;347(5):305313. DOI: 10.1056/NEJMoa020245
  4. 4Lavie CJ, Osman AF, Milani RV, Mehra MR. Body composition and prognosis in chronic systolic heart failure: The obesity paradox. American Journal of Cardiology. 2003;91(7):891894. DOI: 10.1016/S0002-9149(03)00031-6
  5. 5Horwich TB, Fonarow GC. The impact of obesity on survival in patients with heart failure. Heart Failure Monitor. 2002;3:814. DOI: 10.1054/jcaf.2002.0804216
  6. 6Andreotti F, Rio T, Lavorgna A, Coluzzi G, Santucci E, Cecchetti S, Pennestri F, Crea F. Body mass index and cardiovascular events: the “obesity paradox”. Recenti Progressi in Medicina. 2009;100(10):447450.
  7. 7Lavie CJ, Milani RV, Ventura HO. Obesity and the “obesity paradox” in cardiovascular diseases. Clinical Pharmacology & Therapeutics. 2011;90(1):2325. DOI: 10.1038/clpt.2011.87
  8. 8Zafrir B, Adir Y, Shehadeh W, Shteinberg M, Salman N, Amir O. The association between obesity, mortality and filling pressures in pulmonary hypertension patients: The “obesity paradox”. Respiratory Medicine. 2013;107(1):139146. DOI: 10.1016/j.rmed.2012.10.019
  9. 9Stamou SC, Nussbaum M, Stiegel RM, Reames MK, Skipper ER, Robicsek F, Lobdell KW. Effect of body mass index on outcomes after cardiac surgery: Is there an obesity paradox? The Annals of Thoracic Surgery. 2011;91(1):4247. DOI: 10.1016/j.athoracsur.2010.08.047
  10. 10Goel K, Lopez-Jimenez F, De Schutter A, Coutinho T, Lavie CJ. Obesity paradox in different populations: Evidence and controversies. Future Cardiology. 2014;10(1):8191. DOI: 10.2217/fca.13.84
  11. 11Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425432. DOI: 10.1038/372425a0
  12. 12McGaffin KR, Witham WG, Yester KA, Romano LC, O’Doherty RM, McTiernan CF, O’Donnell CP. Cardiac-specific leptin receptor deletion exacerbates ischaemic heart failure in mice. Cardiovascular Research. 2011;89(1):6071. DOI: 10.1093/cvr/cvq288
  13. 13Leyva F, Anker SD, Egerer K, Stevenson JC, Kox WJ, Coats AJ. Hyperleptinaemia in chronic heart failure. Relationships with insulin. European Heart Journal. 1998;19(10):15471551. DOI: 10.1053/euhj.1998.1045
  14. 14El-Bindary EM, Darwish AZ. New biochemical markers in chronic heart failure. East Mediterranean Health Journal. 2001;7(4–5):697706. DOI: 10.26719/2001.7.4-5.697
  15. 15Toth MJ, Gottlieb SS, Fisher ML, Ryan AS, Nicklas BJ, Poehlman ET. Plasma leptin concentrations and energy expenditure in heart failure patients. Metabolism: Clinical and Experimental. 1997;46(4):450453. DOI: 10.1016/S0026-0495(97)90065-2
  16. 16Murdoch DR, Rooney E, Dargie HJ, Shapiro D, Morton JJ, McMurray JJ. Inappropriately low plasma leptin concentration in the cachexia associated with chronic heart failure. Heart. 1999;82(3):352356. DOI: 10.1136/hrt.82.3.352
  17. 17Wells GA, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of non-randomised studies in meta-analyses [Accessed 2014 Aug 5]. Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
  18. 18Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [Accessed 2014 Aug]. Available from: http://www.cochrane-handbook.org.
  19. 19Doehner W, Pflaum CD, Rauchhaus M, Godsland IF, Egerer K, Cicoira M, Florea VG, Sharma R, Bolger AP, Coats AJ, Anker SD, Strasburger CJ. Leptin, insulin sensitivity and growth hormone binding protein in chronic heart failure with and without cardiac cachexia. European Journal of Endocrinology. 2001;145(6):727735. DOI: 10.1530/eje.0.1450727
  20. 20Schulze PC, Kratzsch J, Linke A, Schoene N, Adams V, Gielen S, Erbs S, Moebius-Winkler S, Schuler G. Elevated serum levels of leptin and soluble leptin receptor in patients with advanced chronic heart failure. European Journal of Heart Failure. 2003;5(1):3340. DOI: 10.1016/S1388-9842(02)00177-0
  21. 21McEntegart MB, Awede B, Petrie MC, Sattar N, Dunn FG, MacFarlane NG, McMurray JJ. Increase in serum adiponectin concentration in patients with heart failure and cachexia: Relationship with leptin, other cytokines, and B-type natriuretic peptide. European Heart Journal. 2007;28(7):829835. DOI: 10.1093/eurheartj/ehm033
  22. 22Fernandes F, Dantas S, Ianni BM, Ramires FJA, Buck P, Salemi VMC, Lopes HF, Mady C. Leptin levels in different forms of Chagas’ disease. Brazilian Journal of Medical and Biological Research. 2007;40(12):16311636. DOI: 10.1590/S0100-879X2006005000152
  23. 23Patel JV, Sosin M, Lim HS, Chung I, Panja N, Davis RC, Hughes EA, Lip GYH. Raised leptin concentrations among South Asian patients with chronic heart failure. International Journal of Cardiology. 2007;122(1):3440. DOI: 10.1016/j.ijcard.2006.11.013
  24. 24Sierra-Johnson J, Romero-Corral A, Somers VK, Olson LJ, Johnson BD. Leptin, a novel predictor of lung function in heart failure. Chest. 2008;134(2):346350. DOI: 10.1378/chest.07-2751
  25. 25Straburzyńska-Migaj E, Gwizdała A, Siniawski A, Ochotny R, Grajek S. Leptin and inflammation in patients with chronic heart failure. Kardiologia Polska. 2010;68(11):1243.
  26. 26Schulze PCMP, Biolo AM, Gopal DM, Shahzad KM, Balog JM, Fish MM, Siwik DP, Colucci WSM. Dynamics in insulin resistance and plasma levels of adipokines in patients with acute decompensated and chronic stable heart failure. Journal of Cardiac Failure. 2011;17(12):10041011. DOI: 10.1016/j.cardfail.2011.08.010
  27. 27Bozic B, Loncar G, Prodanovic N, Radojicic Z, Cvorovic V, Dimkovic S, Popovic-Brkic V. Relationship between high circulating adiponectin with bone mineral density and bone metabolism in elderly males with chronic heart failure. Journal of Cardiac Failure. 2010;16(4):301307. DOI: 10.1016/j.cardfail.2009.12.015
  28. 28Karayannis G, Giamouzis G, Tziolas N, Georgoulias P, Skoularigis J, Mikhailidis DP, Triposkiadis F. Association between epicardial fat thickness and weight homeostasis hormones in patients with noncachectic heart failure. Angiology. 2013;64(3):173180. DOI: 10.1177/0003319712447978
  29. 29Loncar G, Bozic B, von Haehling S, Düngen H, Prodanovic N, Lainscak M, Arandjelovic A, Dimkovic S, Radojicic Z, Popovic V. Association of adiponectin with peripheral muscle status in elderly patients with heart failure. European Journal of Internal Medicine. 2013;24(8):818823. DOI: 10.1016/j.ejim.2013.09.011
  30. 30Faxen UL, Hage C, Andreasson A, Donal E, Daubert JC, Linde C, Brismar K, Lund LH. HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and adiponectin. International Journal of Cardiology. 2017;228:709716. DOI: 10.1016/j.ijcard.2016.11.194
  31. 31Shiina Y, Murakami T, Matsumoto N, Okamura D, Takahashi Y, Nishihata Y, Komiyama N, Niwa K. Body composition, appetite-related hormones, adipocytokines, and heart failure in adult patients with congenital heart disease: A preliminary study. Congenital Heart Disease. 2018;13(1):7984. DOI: 10.1111/chd.12555
  32. 32Dabarian AL, Mady C, Barbosa-Ferreira JM, Ianni BM, Hotta VT, Ramires FJA, Lopes HF, Buck PDC, Pessoa FG, Fonseca KCB, Nogueira AR, Fernandes F. Dysregulation of insulin levels in Chagas heart disease is associated with altered adipocytokine levels. Canadian Journal of Physiology and Pharmacology. 2019;97(2):140145. DOI: 10.1139/cjpp-2018-0349
  33. 33Isse N, Ogawa Y, Tamura N, Masuzaki H, Mori K, Okazaki T, Satoh N, Shigemoto M, Yoshimasa Y, Nishi S, Et A. Structural organization and chromosomal assignment of the human obese gene. Journal of Biological Chemistry. 1995;270(46):2772827733. DOI: 10.1074/jbc.270.46.27728
  34. 34Schroeter MR, Schneiderman J, Schumann B, Gluckermann R, Grimmas P, Buchwald AB, Tirilomis T, Schondube FA, Konstantinides SV, Schafer K. Expression of the leptin receptor in different types of vascular lesions. Histochemistry and Cell Biology. 2007;128(4):323333. DOI: 10.1007/s00418-007-0319-1
  35. 35Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, Sewter CP, Digby JE, Mohammed SN, Hurst JA, Cheetham CH, Earley AR, Barnett AH, Prins JB, O’Rahilly S. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903908. DOI: 10.1038/43185
  36. 36Thompson DB, Ravussin E, Bennett PH, Bogardus C. Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. Human Molecular Genetics. 1997;6(5):675679. DOI: 10.1093/hmg/6.5.675
  37. 37Swan JW, Anker SD, Walton C, Godsland IF, Clark AL, Leyva F, Stevenson JC, Coats AJ. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. Journal of American College of Cardiology. 1997;30(2):527532. DOI: 10.1016/S0735-1097(97)00185-X
  38. 38Doehner W, Rauchhaus M, Godsland IF, Egerer K, Niebauer J, Sharma R, Cicoira M, Florea VG, Coats AJ, Anker SD. Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-alpha. International Journal of Cardiology. 2002;83(1):7381. DOI: 10.1016/S0167-5273(02)00022-0
  39. 39Barr VA, Malide D, Zarnowski MJ, Taylor SI, Cushman SW. Insulin stimulates both leptin secretion and production by rat white adipose tissue. Endocrinology. 1997;138(10):44634472. DOI: 10.1210/endo.138.10.5451
  40. 40Larsson H, Ahren B. Short-term dexamethasone treatment increases plasma leptin independently of changes in insulin sensitivity in healthy women. The Journal of Clinical Endocrinology & Metabolism. 1996;81(12):44284432. DOI: 10.1210/jc.81.12.4428
  41. 41Nordfors L, Lonnqvist F, Heimburger O, Danielsson A, Schalling M, Stenvinkel P. Low leptin gene expression and hyperleptinemia in chronic renal failure. Kidney International. 1998;54(4):12671275. DOI: 10.1046/j.1523-1755.1998.00088.x
  42. 42Wannamethee SG, Shaper AG, Whincup PH, Lennon L, Sattar N. Obesity and risk of incident heart failure in older men with and without pre-existing coronary heart disease: Does leptin have a role? Journal of American College of Cardiology. 2011;58(18):18701877. DOI: 10.1016/j.jacc.2011.06.057
  43. 43Pladevall M, Williams K, Guyer H, Sadurni J, Falces C, Ribes A, Pare C, Brotons C, Gabriel R, Serrano-Rios M, Haffner S. The association between leptin and left ventricular hypertrophy: A population-based cross-sectional study. Journal of Hypertension. 2003;21(8):14671473. DOI: 10.1097/00004872-200308000-00009
  44. 44Rajapurohitam V, Gan XT, Kirshenbaum LA, Karmazyn M. The obesity-associated peptide leptin induces hypertrophy in neonatal rat ventricular myocytes. Circulation Research. 2003;93(4):277279. DOI: 10.1161/01.RES.0000089255.37804.72
  45. 45Tajmir P, Ceddia RB, Li RK, Coe IR, Sweeney G. Leptin increases cardiomyocyte hyperplasia via extracellular signal-regulated kinase-and phosphatidylinositol 3-kinase-dependent signaling pathways. Endocrinology. 2004;145(4):15501555. DOI: 10.1210/en.2003-1128
  46. 46Kain D, Simon AJ, Greenberg A, Ben ZD, Gilburd B, Schneiderman J. Cardiac leptin overexpression in the context of acute MI and reperfusion potentiates myocardial remodeling and left ventricular dysfunction. PLoS One. 2018;13(10):e203902. DOI: 10.1371/journal.pone.0203902
  47. 47Mao Y, Zhao K, Li P, Sheng Y. The emerging role of leptin in obesity-associated cardiac fibrosis: Evidence and mechanism. Molecular and Cellular Biochemistry. 2023;478(5):9911011. DOI: 10.1007/s11010-022-04562-6
  48. 48Nickola MW, Wold LE, Colligan PB, Wang GJ, Samson WK, Ren J. Leptin attenuates cardiac contraction in rat ventricular myocytes. Role of NO. Hypertension. 2000;36(4):501505. DOI: 10.1161/01.HYP.36.4.501
  49. 49Katz AM. Maladaptive growth in the failing heart: the cardiomyopathy of overload. Cardiovascular Drugs and Therapy. 2002;16(3):245249. DOI: 10.1023/A:1020604623427
  50. 50Dong F, Zhang X, Ren J. Leptin regulates cardiomyocyte contractile function through endothelin-1 receptor-NADPH oxidase pathway. Hypertension. 2006;47(2):222229. DOI: 10.1161/01.HYP.0000198555.51645.f1
  51. 51Adiarto S, Emoto N, Iwasa N, Yokoyama M. Obesity-induced upregulation of myocardial endothelin-1 expression is mediated by leptin. Biochemical and Biophysical Research Communications. 2007;353(3):623627. DOI: 10.1016/j.bbrc.2006.12.066
  52. 52Na T, Dai DZ, Tang XY, Dai Y. Upregulation of leptin pathway correlates with abnormal expression of SERCA2a, phospholamban and the endothelin pathway in heart failure and reversal by CPU86017. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2007;375(1):3949. DOI: 10.1007/s00210-007-0134-1
  53. 53Zeidan A, Javadov S, Karmazyn M. Essential role of Rho/ROCK-dependent processes and actin dynamics in mediating leptin-induced hypertrophy in rat neonatal ventricular myocytes. Cardiovascular Research. 2006;72(1):101111. DOI: 10.1016/j.cardiores.2006.06.024
  54. 54Zeidan A, Javadov S, Chakrabarti S, Karmazyn M. Leptin-induced cardiomyocyte hypertrophy involves selective caveolae and RhoA/ROCK-dependent p38 MAPK translocation to nuclei. Cardiovascular Research. 2008;77(1):6472. DOI: 10.1093/cvr/cvm020
  55. 55Rubio B, Pintado C, Mazuecos L, Benito M, Andres A, Gallardo N. Central actions of leptin induce an atrophic pattern and improves heart function in lean normoleptinemic rats via PPARbeta/delta activation. Biomolecules. 2024;14(8):1028. DOI: 10.3390/biom14081028
DOI: https://doi.org/10.5334/gh.1434 | Journal eISSN: 2211-8179
Language: English
Submitted on: Oct 10, 2024
Accepted on: May 12, 2025
Published on: May 23, 2025
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2025 Xin Sun, Caihong Xin, Jiayi Yao, Hongli Wang, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.