Cardioprotective properties of leptin in patients with excessive body mass

Aleksandra Paduszyńska, Agata Sakowicz, Maciej Banach, Marek Maciejewski, Marek Dąbrowa, Agata Bielecka-Dąbrowa, Aleksandra Paduszyńska, Agata Sakowicz, Maciej Banach, Marek Maciejewski, Marek Dąbrowa, Agata Bielecka-Dąbrowa

Abstract

Background: Adipose tissue is producing adipokines that play different roles in the pathophysiology of cardiovascular disease.

Aims: The study aimed to assess the role of selected biomarkers in hypertensive patients with overweight and obesity compared with those with normal body-mass index (BMI).

Methods: A total of 62 patients with BMI < 25 kg/m2 (median age 54 (46-58) yrs., 57% males) and 51 with BMI ≥ 25 kg/m2 (median age 53 (48-59) yrs., 37% males) were enrolled. Biochemical parameters, leptin, adiponectin, and resistin; asymmetric dimethylarginine; interleukin 6; and N-terminal propeptide of type III procollagen, were assessed in plasma. The evaluation of hemodynamic parameters was performed using SphygmoCor 9.0 tonometer. Echocardiography was performed using AlokaAlpha 10 Premier device.

Results: Overweight and obese patients had significantly higher concentration of leptin (34 vs 18 ng/ml; p = 0.03), ADMA (0.43 vs 0.38 μmol/l, p = 0.04), and lower concentration of adiponectin (5.3 vs 7 μg/ml, p = 0.01). The only significant difference in tonometry analysis was higher aortic pulse pressure (mmHg) in patients with BMI ≥ 25 kg/m2 group (34 vs 30; p = 0.03). These patients had also significantly lower peak systolic velocity and early diastolic velocity in tissue Doppler imaging of the right ventricle free wall at the level of the tricuspid annulus compared with controls (p = 0.02 and p = 0.001, respectively). The level of leptin is correlated negatively with the left ventricular mass index (LVMI) (R Spearman = - 0.5; p = 0.002) and PWV (R = - 0.4; p = 0.01) and ADMA with total and LDL cholesterol (R = - 0.42; p = 0.008), and adiponectin is correlated positively with HDL cholesterol (R = 0.67; p = 0.0001).

Conclusions: Leptin concentrations were inversely proportional to LVMI and PWV in patients with BMI < 25 kg/m2.

Trial registration: Clinicaltrials.gov study ID: NCT04175080.

Keywords: Adipokines; Hypertrophy; Left ventricular remodeling; Leptin.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
ROC chart for leptin

References

    1. GBD 2015 Obesity Collaborators Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377(1):13–27. doi: 10.1056/NEJMoa1614362.
    1. Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15(4):6184–6223. doi: 10.3390/ijms15046184.
    1. Bielecka-Dąbrowa A, Michalska-Kasiczak M, Gluba A, et al. Biomarkers and echocardiographic predictors of myocardial dysfunction in patients with hypertension. Sci Rep. 2015;5:8916. doi: 10.1038/srep08916.
    1. Bielecka-Dąbrowa A, Gluba-Brzózka A, Michalska-Kasiczak M, et al. The multi-biomarker approach for heart failure in patients with hypertension. Int J Mol Sci. 2015;16(5):10715–10733. doi: 10.3390/ijms160510715.
    1. Kapłon-Cieślicka A, Postuła M, Rosiak M, et al. Association of adipokines and inflammatory markers with lipid control in type 2 diabetes. Pol Arch Med Wewn. 2015;125(6):414–423. doi: 10.20452/pamw.2880.
    1. Borges MC, Barros AJD, Ferreira DLS, Casas JP, Horta BL, Kivimaki M, Kumari M, Menon U, Gaunt TR, Ben-Shlomo Y, Freitas DF, Oliveira IO, Gentry-Maharaj A, Fourkala E, Lawlor DA, Hingorani AD. Metabolic profiling of adiponectin levels in adults: Mendelian randomization analysis. Circ Cardiovasc Genet. 2017;10(6):e001837. doi: 10.1161/CIRCGENETICS.117.001837.
    1. Nishiyama Y, Ueda M, Katsura K et al (2010) Asymmetric dimethylarginine (adma) as a possible risk marker for ischemic stroke. J Neurol Sci 290(1-2):12–15. 10.1016/j.jns.2009.12.020.epub2010jan8
    1. Fliser D. Asymmetric dimethylarginine (adma): the silent transition from an ‘uraemic toxin’ to a global cardiovascular risk molecule. Eur J Clin Investig. 2005;35(2):71–79. doi: 10.1111/j.1365-2362.2005.01457.x.
    1. Stępień M, Stępień A, Banach M, et al. New obesity indices and adipokines in normotensive patients and patients with hypertension: comparative pilot analysis. Angiology. 2014;65(4):333–342. doi: 10.1177/0003319713485807.
    1. Stępień M, Stępień A, Wlazeł RN, Paradowski M, Banach M, Rysz M, Rysz J. Obesity indices and adipokines in non-diabetic obese patients with early stages of chronic kidney disease. Med Sci Monit. 2013;19:1063–1072. doi: 10.12659/MSM.889390.
    1. Mechanick JI, Zhao S, Garvey WT. The adipokine-cardiovascular-lifestyle network: translation to clinical practice. J Am Coll Cardiol. 2016;68(16):1785–1803. doi: 10.1016/j.jacc.2016.06.072.
    1. Mechanick JI, Zhao S, Garvey WT. Leptin, an adipokine with central importance in the global obesity problem. Glob Heart. 2018;13(2):113–127. doi: 10.1016/j.gheart.2017.10.003.
    1. Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovascular disease and type 2 diabetes mellitus. Acta Pharmacol Sin. 2018;39(7):1176–1188. doi: 10.1038/aps.2018.40.
    1. Rajapurohitam V, Gan XT, Kirshenbaum LA, Karmazyn M. The obesity-associated peptide leptin induces hypertrophy in neonatal rat ventricular myocytes. Circ Res. 2003;93(4):277–279. doi: 10.1161/01.RES.0000089255.37804.72.
    1. Tajmir 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):1550–1555. doi: 10.1210/en.2003-1128.
    1. Barouch LA, Berkowitz DE, Harrison RW, O'Donnell CP, Hare JM. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation. 2003;108(6):754–759. doi: 10.1161/01.CIR.0000083716.82622.FD.
    1. McGaffin KR, Sun CK, Rager JJ, Romano LC, Zou B, Mathier MA, O'Doherty RM, McTiernan C, O'Donnell CP. Leptin signalling reduces the severity of cardiac dysfunction and remodeling after chronic ischaemic injury. Cardiovasc Res. 2008;77(1):54–63. doi: 10.1093/cvr/cvm023.
    1. Faxén 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. Int J Cardiol. 2017;228:709–716. doi: 10.1016/j.ijcard.2016.11.194.
    1. Sahu A. Minireview: a hypothalamic role in energy balance with special emphasis on leptin. Endocrinology. 2004;145(6):2613–2620. doi: 10.1210/en.2004-0032.
    1. Martin SS, Blaha MJ, Muse ED, Qasim AN, Reilly MP, Blumenthal RS, Nasir K, Criqui MH, McClelland R, Hughes-Austin JM, Allison MA. Leptin and incident cardiovascular disease: the multi-ethnic study of atherosclerosis (MESA) Atherosclerosis. 2015;239(1):67–72. doi: 10.1016/j.atherosclerosis.2014.12.033.
    1. Paolisso G, Taglaimonte MR, Galderisi M, et al. Plasma leptin concentration, insulin sensitivity, and 24-hour ambulatory blood pressure and left ventricular geometry. Am J Hypertens. 2001;14(2):114–120. doi: 10.1016/S0895-7061(00)01241-3.
    1. Paolisso G, Tagliamonte MR, Galderisi M, Zito GA, Petrocelli A, Carella C, de Divitiis O, Varricchio M. Plasma leptin level is associated with myocardial wall thickness in hypertensive insulin-resistant men. Hypertension. 1999;34(5):1047–1052. doi: 10.1161/01.HYP.34.5.1047.
    1. Perego L, Pizzocri P, Corradi D, Maisano F, Paganelli M, Fiorina P, Barbieri M, Morabito A, Paolisso G, Folli F, Pontiroli AE. Circulating leptin correlates with left ventricular mass in morbid (grade III) obesity before and after weight loss induced by bariatric surgery: a potential role for leptin in mediating human left ventricular hypertrophy. J Clin Endocrinol Metab. 2005;90(7):4087–4093. doi: 10.1210/jc.2004-1963.
    1. Vasan RS, Levy D. The role of hypertension in the pathogenesis of heart failure. A clinical mechanistic overview. Arch Intern Med. 1996;156(16):1789–1796. doi: 10.1001/archinte.1996.00440150033003.
    1. Mark AL. Selective leptin resistance revisited. Am J Phys Regul Integr Comp Phys. 2013;305(6):R566–R581. doi: 10.1152/ajpregu.00180.2013.
    1. Kain D, Simon AJ, Greenberg A, Ben Zvi D, Gilburd B, Schneiderman J. Cardiac leptin overexpression in the context of acute MI and reperfusion potentiates myocardial remodelling and left ventricular dysfunction. PLoS One. 2018;13(10):e0203902. doi: 10.1371/journal.pone.0203902.
    1. Windham BG, Griswold ME, Farasat SM, Ling SM, Carlson O, Egan JM, Ferrucci L, Najjar SS. Influence of leptin, adiponectin, and resistin on the association between abdominal adiposity and arterial stiffness. Am J Hypertens. 2010;23(5):501–507. doi: 10.1038/ajh.2010.8.
    1. Kamimura D, Suzuki T, Wang W, deShazo M, Hall JE, Winniford MD, Kullo IJ, Mosley TH, Butler KR, Hall ME. Higher plasma leptin levels are associated with reduced left ventricular mass and left ventricular diastolic stiffness in black women: insights from the genetic epidemiology network of Arteriopathy (GENOA) study. Hypertens Res. 2018;41(8):629–638. doi: 10.1038/s41440-018-0062-0.
    1. Lieb W, Sullivan LM, Aragam J, et al. Relation of serum leptin with cardiac mass and left atrial dimension in individuals >70 years of age. Am J Cardiol. 2009;104(4):602–605. doi: 10.1016/j.amjcard.2009.04.026.

Source: PubMed

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