Relationship Between Ob Gene Product and Lipid Profile in The Pathogenesis of Atherosclerosis

Mathangi R¹, Selvaraj J², Reji M³, Jaideep M⁴, Ponnulakshmi R⁵, Nalini D^4*, Samyuktha. P⁶, Pugazharasan⁶

In the present study, we investigated the role of leptin in the pathogenesis of atherosclerosis by measuring its levels in atherosclerosis subjects and analyzing its correlation to anthropometric variables such as waist to hip ratio, body mass index, biochemical parameters such as lipids and glucose. Leptin levels correlate to serum glucose, triglycerides, waist to hip ratio, body mass index, and blood pressure in atherosclerosis subjects with increased body mass index. Our results show that leptin influences the lipid profile to induce the pathogenesis of atherosclerosis.

Abstract

Leptin, Ob gene product is overexpressed in atherosclerotic lesions, and leptin signaling is implicated in promoting both thrombosis and atherosclerosis in mice models, suggesting a role for leptin in CVD. Leptin is also known to promote pro-inflammatory signaling through cytokines and growth factors that may contribute to the progression of atherosclerosis. Hence, in the present study, we investigated the role of leptin in the pathogenesis of atherosclerosis by measuring its levels in atherosclerosis subjects and analyzing its correlation to anthropometric variables such as waist to hip ratio, body mass index, and biochemical parameters as lipids and glucose. Leptin levels correlate to serum glucose, triglycerides, waist to hip ratio, body mass index, and blood pressure in atherosclerosis subjects with increased body mass index. Our results show that leptin influences the lipid profile to induce the pathogenesis of atherosclerosis.

Keywords: leptin, lipid profile, glucose, atherosclerosis, body mass index

References

Agha M, Agha R. The rising prevalence of obesity: part A: impact on public health. Int J Surg Oncol (N Y). 2017;2(7):e17.

https://doi.org/10.1097/IJ9.0000000000000017

Babu S, Krishnan M, Rajagopal P, Periyasamy V, Veeraraghavan V, Govindan R, Jayaraman S. Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats. Eur J Pharmacol. 2020: 15;873:173004.

https://doi.org/10.1016/j.ejphar.2020.173004

Beamount, J.L, CrisonLA, Coope, G.R, Feifar Z, Frederickson D.S, Strasser, T. 1972. Classification of Hyper-lipidemias and Hyperlipoproteinemias. Standard Methods of Clinical Chemistry, Academic Press, New York, 9.

Chandrasekaran Kirubhanand, Jayaraman Selvaraj, Umapathy Vidhya Rekha, Veeraraghavan Vishnupriya, Venkatachalam Sivabalan, Mathayan Manikannan, Devarajan Nalini, Periyasamy, Vijayalakshmi, Manikkam Rajalakshmi, Rajagopal Ponnulakshmi.Molecular docking analysis of Bcl-2 with phytocompounds. Bioinformation. 2020;16(6); 468-473.

https://doi.org/10.6026/97320630016468

Cole T.G., Klotzsch, S.G, Mc Namara, J.Measurement of Triglyceride Concentration. Handbook of Lipoprotein Testing. 1997;AACC Press, Washington DC.

D. Kannan1, L. Pari, E. Paari, T. Gunaseelan, B. Tulsi, Deepak Singh, J. Selvaraj, V. Vishnupriya, R. Ponnulakshmi, B. Shyamaladevi, K. Madhan. Changes in glycoprotein components in high-fat diet induced type 2 diabetes: Influence of cuminaldehyde Drug Invention Today.2018; 10(5): 3740-3745.

D.Nalini, P.Hema and Selvaraj J. Pro-inflammatory role of leptin in peripheral blood mononuclear cells. Drug Invention Today.2019; 12: 2381-2384.

Dardeno TA, Chou SH, Moon HS, Chamberland JP, Fiorenza CG, Mantzoros CS. Leptin in human physiology and therapeutics. Front Neuroendocrinol. 2010 ;31(3):377-93..

https://doi.org/10.1016/j.yfrne.2010.06.002

Devarajan N, Jayaraman S, Mahendra J, Venkatratnam P, Rajagopal P, Palaniappan H, Ganesan SK. Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies. Phytother Res. 2021.

https://doi.org/10.1002/ptr.7032

El Haouari M, Rosado JA. Phytochemical, Anti-diabetic and Cardiovascular Properties of Urtica dioica L. (Urticaceae): A Review. Mini Rev Med Chem. 2019;19(1):63-71.

https://doi.org/10.2174/1389557518666180924121528

Elsayed EF, Tighiouart H, Weiner DE, Griffith J, Salem D, Levey AS, Sarnak MJ. Waist-to-hip ratio and body mass index as risk factors for cardiovascular events in CKD. Am J Kidney Dis. 2008 ;52(1):49-57.

https://doi.org/10.1053/j.ajkd.2008.04.002

Golia E, Limongelli G, Natale F, Fimiani F, Maddaloni V, Russo PE, Riegler L, Bianchi R, Crisci M, Palma GD, Golino P, Russo MG, Calabrò R, Calabrò P. Adipose tissue and vascular inflammation in coronary artery disease. World J Cardiol. 2014 26;6(7):539-54.

Gomez-Delgado F, Katsiki N, Lopez-Miranda J, Perez-Martinez P. Dietary habits, lipoprotein metabolism and cardiovascular disease: From individual foods to dietary patterns. Crit Rev Food Sci Nutr. 2021;61(10):1651-1669.

https://doi.org/10.1080/10408398.2020.1764487

Hema P, Selvaraj J, D.Nalini. Hypolipidemic properties of Aloe vera in female Swiss albino mice. Drug Invention Today.2019; 12: 2377-2380.

https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)

Jayaraman S, Devarajan N?, Rajagopal P. β-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKβ/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats. Molecules. 2021;26(7):2101.

https://doi.org/10.3390/molecules26072101

Kim HW, Shi H, Winkler MA, Lee R, Weintraub NL. Perivascular Adipose Tissue and Vascular Perturbation/Atherosclerosis. Arterioscler Thromb Vasc Biol. 2020;40(11):2569-2576.

https://doi.org/10.1161/ATVBAHA.120.312470

Ku IA, Farzaneh-Far R, Vittinghoff E, Zhang MH, Na B, Whooley MA. Association of low leptin with cardiovascular events and mortality in patients with stable coronary artery disease: the Heart and Soul Study. Atherosclerosis. 2011;217(2):503-508. doi:10.1016/j.atherosclerosis.2010.10.047

https://doi.org/10.1016/j.atherosclerosis.2010.10.047

Lovren F, Teoh H, Verma S. Obesity and atherosclerosis: mechanistic insights. Can J Cardiol. 2015 ;31(2):177-83.

https://doi.org/10.1016/j.cjca.2014.11.031

N.Shanthi, R.Mani, Nalini Devarajan, P.Hema, G.S.Thiriveni Balajji. Leptin - An immunomodulator in Peripheral Blood Mononuclear Cells. IOSR Journal of Dental and Medical Sciences. Vol.2016;15. 52-57.

Nalini D, Karthick R, Shirin V, Manohar G, and Malathi R . Leptin - A possible link between Obesity, Inflammation and Cardiovascular Diseases, Thrombosis Journal.2015; 13:1-7.

https://doi.org/10.1186/s12959-015-0042-4

Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014 ;384(9943):626-635.

https://doi.org/10.1016/S0140-6736(14)61177-6

Ponnulakshmi R, Shyamaladevi B, Vijayalakshmi P, Selvaraj J. In silico and in vivo analysis to identify the antidiabetic activity of beta sitosterol in adipose tissue of high fat diet and sucrose induced type-2 diabetic experimental rats. Toxicol Mech Methods. 2019;29(4):276-290.

https://doi.org/10.1080/15376516.2018.1545815

R. Raskin Erusan,, D. Nalini., and R. Malathi. Obesity, inflammation and metabolic disorders. Indian Journal of Science and Technology.2008; 1, 1-5.

https://doi.org/10.17485/ijst/2008/v1i4.8

Rajagopal R., Devarajan N., Ganesan M, Raghunathan M.Correlation between Obesity and Inflammation in Cardiovascular Diseases-Evaluation of Leptin and Inflammatory Cytokines. Open Journal of Endocrine and Metabolic Diseases.2012: 2, 7-15.

https://doi.org/10.4236/ojemd.2012.22002

Rajendran K, Devarajan N, Ganesan M,Ragunathan M. Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population, Thrombosis Journal.2012; 10, 1-6.

https://doi.org/10.1186/1477-9560-10-13

Redinger RN. The pathophysiology of obesity and its clinical manifestations. Gastroenterol Hepatol (N Y). 2007;3(11):856-863.

Rocha, V., Libby, P. Obesity, inflammation, and atherosclerosis. Nat Rev Cardiol.2009;6:399-409.

https://doi.org/10.1038/nrcardio.2009.55

Trinder, P.Determination of Blood Glucose Using 4- Aminophenazone. J Clin Pathol, 1959;22, 246.

https://doi.org/10.1136/jcp.22.2.246-b

Young, D.S. (2000) Effects of drugs on clinical laboratory tests, 5th ed. AACC Press