Skip to main content
Top
Published in: Thrombosis Journal 1/2015

Open Access 01-12-2015 | Original clinical investigation

“Role of the adipocyte hormone leptin in cardiovascular diseases – a study from Chennai based Population”

Authors: Devarajan Nalini, Rajendran Karthick, Vijay Shirin, Ganesan Manohar, Raghunathan Malathi

Published in: Thrombosis Journal | Issue 1/2015

Login to get access

Abstract

Background

Obesity is currently regarded as a pro-inflammatory condition during which leptin (Ob gene product) might act as a risk factor for Cardiovascular Diseases (CVD) including Acute Myocardial Infarction (AMI). There is a marked increase in circulating leptin concentrations and inflammatory markers such as Tumor Necrosis Factor-α (TNF-α) in AMI patients but still the association of leptin with inflammation during AMI is not known. The present study suggest that elevated levels of leptin might elicit the risk for CVD by signaling for the secretion of inflammatory cytokines especially, TNF-α.

Methods

Blood samples were collected from 100 CVD subjects diagnosed for AMI immediately after their admission to the hospital and serum leptin, insulin, glucose, lipids and inflammatory marker such as TNF-α were measured. 5 ml random (non-fasting) blood was collected from 100 non-CVD (control) subjects and the results obtained in case of AMI subjects were compared with that of the control subjects. The subjects under study included both men and women belonging to the age group of 35 – 75 and they were classified based on their BMI as normal weight, overweight and obese.

Results

Circulating levels of leptin are found to be elevated in obese control subjects and in patients with AMI irrespective of their Body Mass Index (BMI). In addition, leptin is also found to be positively correlated to serum triglycerides, insulin and TNF-α in AMI subjects. MANOVA analysis suggests that leptin might influence the synthesis of insulin and TNF-α. This is the first report relating leptin to TNF-α in Chennai based population, India.

Conclusions

Hyperleptinemia might act as a risk marker for AMI. The present study suggests that at elevated levels, leptin may favor atherosclerosis by promoting the synthesis of TNF-α and insulin. However, our report warrants further investigation both in vitro and in vivo to determine the exact mechanism behind the pro-atherogenic role of leptin. The observed positive correlation between leptin and BMI in both AMI and control subjects suggests that obese subjects manifest leptin resistance and hence, they possess a greater risk for the incidence of CVD.
Literature
1.
go back to reference Wang Z, Nakayama T. Inflammation, a Link between Obesity and Cardiovascular Disease. Mediat Inflamm. 2010;2010:1–17.CrossRef Wang Z, Nakayama T. Inflammation, a Link between Obesity and Cardiovascular Disease. Mediat Inflamm. 2010;2010:1–17.CrossRef
2.
go back to reference Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;28:499–511.CrossRef Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;28:499–511.CrossRef
3.
go back to reference Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.CrossRefPubMed Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.CrossRefPubMed
4.
go back to reference Considine RV, Considine EL, Williams CJ, Nyce MR, Magosin SA, Bauer TL, et al. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest. 1995;95:2986–8.CrossRefPubMedCentralPubMed Considine RV, Considine EL, Williams CJ, Nyce MR, Magosin SA, Bauer TL, et al. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest. 1995;95:2986–8.CrossRefPubMedCentralPubMed
7.
go back to reference Soderberg S, Ahren B, Jansson JH, Johnson O, Hallmans G, Asplund K, et al. Leptin is associated with increased risk of myocardial infarction. J Intern Med. 1999;246:409–18.CrossRefPubMed Soderberg S, Ahren B, Jansson JH, Johnson O, Hallmans G, Asplund K, et al. Leptin is associated with increased risk of myocardial infarction. J Intern Med. 1999;246:409–18.CrossRefPubMed
8.
go back to reference Leyva F, Anker SD, Egerer K, Stevenson JC, Kox WJ, Coats AJ. Hyperleptinaemia in chronic heart failure. Relationships with insulin. Eur Heart J. 1998;19:1547–51.CrossRefPubMed Leyva F, Anker SD, Egerer K, Stevenson JC, Kox WJ, Coats AJ. Hyperleptinaemia in chronic heart failure. Relationships with insulin. Eur Heart J. 1998;19:1547–51.CrossRefPubMed
9.
go back to reference Krasnodebski P, Bak MI, Opolski G, Karnafel W. Leptin in acute myocardial infarction and period of convalescence in patients with type 2 diabetes mellitus. Kardiol Pol. 2010;68:648–53.PubMed Krasnodebski P, Bak MI, Opolski G, Karnafel W. Leptin in acute myocardial infarction and period of convalescence in patients with type 2 diabetes mellitus. Kardiol Pol. 2010;68:648–53.PubMed
10.
go back to reference Sattar N, Wannamethee G, Sarwar N, Chernova J, Lawlor DA, Kelly A, et al. Leptin and coronary heart disease: prospective study and systematic review. J Am Coll Cardiol. 2009;53:167–75.CrossRefPubMed Sattar N, Wannamethee G, Sarwar N, Chernova J, Lawlor DA, Kelly A, et al. Leptin and coronary heart disease: prospective study and systematic review. J Am Coll Cardiol. 2009;53:167–75.CrossRefPubMed
11.
go back to reference Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001;104:3052–6.CrossRefPubMed Wallace AM, McMahon AD, Packard CJ, Kelly A, Shepherd J, Gaw A, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001;104:3052–6.CrossRefPubMed
12.
go back to reference Tamer L, Ercan B, Unlu A, Sucu N, Pekdemir H, Eskandari G, et al. The relationship between leptin and lipids in atherosclerosis. Indian Heart J. 2002;54:692–6.PubMed Tamer L, Ercan B, Unlu A, Sucu N, Pekdemir H, Eskandari G, et al. The relationship between leptin and lipids in atherosclerosis. Indian Heart J. 2002;54:692–6.PubMed
13.
go back to reference Karthick R, Nalini D, Manohar G, Malathi R. Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population. Thromb J. 2012;10:1–6. Karthick R, Nalini D, Manohar G, Malathi R. Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population. Thromb J. 2012;10:1–6.
14.
go back to reference Raskin Erusan R, Nalini D, Malathi R. Correlation between obesity and inflammation in Cardiovascular Diseases – Evaluation of leptin and inflammatory cytokines. Open Journal of Endocrinology and Metabolic Diseases. Open J Endocr Metab Dis. 2012;2:7–15.CrossRef Raskin Erusan R, Nalini D, Malathi R. Correlation between obesity and inflammation in Cardiovascular Diseases – Evaluation of leptin and inflammatory cytokines. Open Journal of Endocrinology and Metabolic Diseases. Open J Endocr Metab Dis. 2012;2:7–15.CrossRef
15.
go back to reference Shen J, Sakaida I, Uchida K, Terai S, Okita K. Leptin enhances TNF-α production via p38 and JNK MAPK in LPS-stimulated Kupffer cells. Life Sci. 2005;77:1502–15.CrossRefPubMed Shen J, Sakaida I, Uchida K, Terai S, Okita K. Leptin enhances TNF-α production via p38 and JNK MAPK in LPS-stimulated Kupffer cells. Life Sci. 2005;77:1502–15.CrossRefPubMed
16.
go back to reference Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, et al. Leptin regulates proinflammatory immune responses. FASEB J. 1998;12:57–65.PubMed Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, et al. Leptin regulates proinflammatory immune responses. FASEB J. 1998;12:57–65.PubMed
17.
go back to reference Berg AH, Scherer PE. Adipose Tissue, Inflammation, and Cardiovascular Disease. Circ Res. 2005;96:939–49.CrossRefPubMed Berg AH, Scherer PE. Adipose Tissue, Inflammation, and Cardiovascular Disease. Circ Res. 2005;96:939–49.CrossRefPubMed
18.
go back to reference Hotamisligil GS. Mechanisms of TNF-alpha-induced insulin resistance. Exp Clin Endocrinol Diabetes. 1999;107:119–25.CrossRefPubMed Hotamisligil GS. Mechanisms of TNF-alpha-induced insulin resistance. Exp Clin Endocrinol Diabetes. 1999;107:119–25.CrossRefPubMed
19.
go back to reference Nieto-Vazquez I, Fernández-Veledo S, Krämer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem. 2008;114:183–94.CrossRefPubMed Nieto-Vazquez I, Fernández-Veledo S, Krämer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem. 2008;114:183–94.CrossRefPubMed
20.
go back to reference Trinder P. Determination of Blood Glucose Using 4- Aminophenazone. J Clin Pathol. 1959;22:246.CrossRef Trinder P. Determination of Blood Glucose Using 4- Aminophenazone. J Clin Pathol. 1959;22:246.CrossRef
21.
go back to reference Cole TG, Klotzsch SG, Mc Namara J. Measurement of Triglyceride Concentration. In: Handbook of Lipoprotein Testing. Washington DC: AACC Press; 1997. Cole TG, Klotzsch SG, Mc Namara J. Measurement of Triglyceride Concentration. In: Handbook of Lipoprotein Testing. Washington DC: AACC Press; 1997.
22.
go back to reference Beamount JL, Crison LA, Coope GR, Feifar Z, Frederickson DS, Strasser T. Classification of Hyper-lipidemias and Hyperlipoproteinemias. In: Standard Methods of Clinical Chemistry. New York: Academic Press; 1972. p. 9. Beamount JL, Crison LA, Coope GR, Feifar Z, Frederickson DS, Strasser T. Classification of Hyper-lipidemias and Hyperlipoproteinemias. In: Standard Methods of Clinical Chemistry. New York: Academic Press; 1972. p. 9.
23.
go back to reference Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Xavier Pi-Sunyer F, et al. Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss: An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898–918.CrossRefPubMed Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Xavier Pi-Sunyer F, et al. Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss: An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898–918.CrossRefPubMed
24.
go back to reference Yang R, Barouch LA. Leptin signaling and obesity - Cardiovascular Consequences. Circ Res. 2007;101:545–59.CrossRefPubMed Yang R, Barouch LA. Leptin signaling and obesity - Cardiovascular Consequences. Circ Res. 2007;101:545–59.CrossRefPubMed
26.
go back to reference Singh M, Bedi US, Singh PP, Arora R, Khosla S. Leptin and the clinical cardiovascular risk. Int J Cardiol. 2010;140:266–71.CrossRefPubMed Singh M, Bedi US, Singh PP, Arora R, Khosla S. Leptin and the clinical cardiovascular risk. Int J Cardiol. 2010;140:266–71.CrossRefPubMed
27.
go back to reference Werner N, Nickenig G. From fat fighter to risk factor: the zigzag trek of leptin. Arterioscler Thromb Vasc Biol. 2004;24:7–9.CrossRefPubMed Werner N, Nickenig G. From fat fighter to risk factor: the zigzag trek of leptin. Arterioscler Thromb Vasc Biol. 2004;24:7–9.CrossRefPubMed
28.
go back to reference Konstantinides S, Schäfer K, Koschnick S, Loskutoff DJ. Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J Clin Invest. 2001;108:1533–40.CrossRefPubMedCentralPubMed Konstantinides S, Schäfer K, Koschnick S, Loskutoff DJ. Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J Clin Invest. 2001;108:1533–40.CrossRefPubMedCentralPubMed
29.
go back to reference Bodary PF, Westrick RJ, Wickenheiser KJ, Shen Y, Eitzman DT. Effect of leptin on arterial thrombosis following vascular injury in mice. JAMA. 2002;287:1706–9.CrossRefPubMed Bodary PF, Westrick RJ, Wickenheiser KJ, Shen Y, Eitzman DT. Effect of leptin on arterial thrombosis following vascular injury in mice. JAMA. 2002;287:1706–9.CrossRefPubMed
30.
go back to reference Correia ML, Haynes WG. Leptin, obesity and cardiovascular disease. Curr Opin Nephrol Hypertens. 2004;13:215–23.CrossRefPubMed Correia ML, Haynes WG. Leptin, obesity and cardiovascular disease. Curr Opin Nephrol Hypertens. 2004;13:215–23.CrossRefPubMed
31.
32.
go back to reference Olstad R, Florholmen J, Svartberg J, Rosenvinge JH, Birketvedt GS. Leptin in the General Population, Differences in Sex Hormones, Blood Lipids, Gender and Life Style Characteristics. Open Behav Sci J. 2011;5:8–15.CrossRef Olstad R, Florholmen J, Svartberg J, Rosenvinge JH, Birketvedt GS. Leptin in the General Population, Differences in Sex Hormones, Blood Lipids, Gender and Life Style Characteristics. Open Behav Sci J. 2011;5:8–15.CrossRef
33.
go back to reference Reaven GM. Insulin Resistance/Compensatory Hyperinsulinemia, Essential Hypertension, and Cardiovascular Disease. J Endocrinol Metab. 2003;88:2399–403.CrossRef Reaven GM. Insulin Resistance/Compensatory Hyperinsulinemia, Essential Hypertension, and Cardiovascular Disease. J Endocrinol Metab. 2003;88:2399–403.CrossRef
34.
go back to reference Russo C, Polosa R. TNF-alpha as a promising therapeutic target in chronic asthma: a lesson from rheumatoid arthritis. Clin Sci (Lond). 2005;109:135–42.CrossRef Russo C, Polosa R. TNF-alpha as a promising therapeutic target in chronic asthma: a lesson from rheumatoid arthritis. Clin Sci (Lond). 2005;109:135–42.CrossRef
36.
go back to reference Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and Cardiovascular Disease : A Scientific Statement From the American Heart Association. Circulation. 2011;123:2292–333.CrossRefPubMed Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and Cardiovascular Disease : A Scientific Statement From the American Heart Association. Circulation. 2011;123:2292–333.CrossRefPubMed
37.
go back to reference Chait A, Brazg RL, Tribble DL, Krauss RM. Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. Am J Med. 1993;94:350–6.CrossRefPubMed Chait A, Brazg RL, Tribble DL, Krauss RM. Susceptibility of small, dense, low-density lipoproteins to oxidative modification in subjects with the atherogenic lipoprotein phenotype, pattern B. Am J Med. 1993;94:350–6.CrossRefPubMed
38.
go back to reference Kwiterovich Jr PO. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. Am J Cardiol. 2002;90:30–47.CrossRef Kwiterovich Jr PO. Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. Am J Cardiol. 2002;90:30–47.CrossRef
Metadata
Title
“Role of the adipocyte hormone leptin in cardiovascular diseases – a study from Chennai based Population”
Authors
Devarajan Nalini
Rajendran Karthick
Vijay Shirin
Ganesan Manohar
Raghunathan Malathi
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2015
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-015-0042-4

Other articles of this Issue 1/2015

Thrombosis Journal 1/2015 Go to the issue

Reviewer acknowledgement

Reviewer acknowledgement 2014