期刊论文详细信息
Journal of Diabetes & Metabolic Disorders
Association between hyperleptinemia and oxidative stress in obese diabetic subjects
Kavitha Thirumurugan2  Ethirajan Thirumurugan1  Hansi Priscilla David2  Mohamed Sham Shihabudeen2  Gautam Pandey2 
[1] Palar Hospital, Senthil Clinic & Lab, Gudiyattam, India;Centre for Biomedical Research, School of Bio Sciences & Technology, 206, Structural Biology Lab, VIT University, Vellore, India
关键词: Obesity;    Type 2 diabetes;    Protein carbonyl groups;    Superoxide dismutase;    Glutathione peroxidase;    Malondialdehyde;    Leptin;   
Others  :  1173882
DOI  :  10.1186/s40200-015-0159-9
 received in 2014-10-10, accepted in 2015-04-07,  发布年份 2015
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【 摘 要 】

Background

Obesity is a worldwide metabolic disorder affecting all types of people. The mechanism by which increased body fat mass that leads to insulin resistance and type 2 diabetes is not yet clearly known. There is a possible crosstalk between leptin, an adipokine and insulin signaling. Leptin mediates insulin sensitivity in hepatocytes; however, its concentration has found to be increased in obese and diabetic subjects. These subjects also have high incidence of oxidative stress status. Therefore, knowing the level of leptin present in obese diabetic subjects will be informative along with its relation to oxidative stress.

Methods

A small population study was performed to explore the association between leptin concentration and oxidative stress status in control and obese type 2 diabetic subjects. Oxidative stress status parameters like malondialdehyde (MDA), superoxide dismutase activity (SOD), glutathione peroxidase activity (GSH-Px), and protein carbonyl (PCO) groups content was measured spectrophotometrically in serum of 43 subjects. Serum Leptin concentration was measured by quantikine sandwich ELISA assay.

Results

The strong positive correlation between MDA (malondialdehyde) and leptin in obese diabetic patients (ρ = 0.787, P < 0.05) suggests close association between lipid peroxidation and hyperleptinemia. In addition, observed positive correlation between protein carbonyl groups and leptin level in obese diabetic subjects (ρ = 0.599, P = 0.001) suggest that hyperleptinemia might also be associated with increased protein oxidation. In multiple logistic regression analysis, leptin has shown a significant association with obese type 2 diabetes [odds ratio (OR): 1.161, 95% confidence interval (Cl): 1.027-1.312, P < 0.05], but the significance is lost after adjusting for Age, BMI, MDA and anti-oxidant parameters.

Conclusions

In the subjects with both obesity and diabetes, there is a significant degree of association between hyperleptinemia and oxidative stress. This association reinforces the existing understanding that obese subjects who also have diabetes are vulnerable to cardiovascular complications driven by increased oxidative stress and hyperleptinemia.

【 授权许可】

   
2015 Pandey et al.; licensee BioMed Central.

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【 参考文献 】
  • [1]Whiting DR, Guariguata L, Weil C, Shaw J: IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011, 94(3):311-21.
  • [2]Fruhbeck G, Gomez-Ambrosi J, Muruzabal FJ, Burrell MA: The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am J Physiol Endocrinol Metab 2001, 280(6):E827-47.
  • [3]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(6505):425-32.
  • [4]MacDougald OA, Hwang CS, Fan H, Lane MD: Regulated expression of the obese gene product (leptin) in white adipose tissue and 3 T3-L1 adipocytes. Proc Natl Acad Sci U S A 1995, 92(20):9034-7.
  • [5]Müller G, Ertl J, Gerl M, Preibisch G: Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem 1997, 272(16):10585-93.
  • [6]Zhao AZ, Shinohara MM, Huang D, Shimizu M, Eldar-Finkelman H, Krebs EG, et al.: Leptin induces insulin-like signaling that antagonizes cAMP elevation by glucagon in hepatocytes. J Biol Chem 2000, 275(15):11348-54.
  • [7]Maffei M, Halaas J, Ravussin E, Pratley R, Lee G, Zhang Y, et al.: Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995, 1(11):1155-61.
  • [8]Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al.: Serum immunoreactive-leptin concentrations in normal-weight and obese humans. New Engl J Med 1996, 334(5):292-5.
  • [9]Okumura T, Taniguchi A, Nagasaka S, Sakai M, Fukushima M, Kuroe A, et al.: Relationship of regional adiposity to serum leptin level in nonobese Japanese type 2 diabetic male patients. Diabetes Metab 2003, 29(1):15-8.
  • [10]Ajala MO, Ogunro PS, Idogun SE, Osundeko O: Relationship between Plasma Antioxidant Status and Leptin in Controlled and Non‐Controlled Type 2 Diabetic Non‐Obese Women. Int J Endocrinol Metabol 2009, 4:214-21.
  • [11]Stefanović A, Kotur-Stevuljević J, Spasić S, Bogavac-Stanojević N, Bujisić N: The influence of obesity on the oxidative stress status and the concentration of leptin in type 2 diabetes mellitus patients. Diabetes Res Clin Pract 2008, 79(1):156-63.
  • [12]Yamagishi SI, Edelstein D, Du XL, Kaneda Y, Guzmán M, Brownlee M: Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem 2001, 276(27):25096-100.
  • [13]Hu FB, Stampfer MJ: Is type 2 diabetes mellitus a vascular condition? Arterioscler Thromb Vasc Biol 2003, 23:1715-6.
  • [14]Lipinski B: Pathophysiology of oxidative stress in diabetes mellitus. J Diabetes Complications 2001, 15(4):203-10.
  • [15]Kuyvenhoven J, Meinders A: Oxidative stress and diabetes mellitus: Pathogenesis of long-term complications. Eur J Intern Med 1999, 10(1):9-19.
  • [16]Sáinz N, Rodríguez A, Catalán V, Becerril S, Ramírez B, Gomez-Ambrosi J et al. Leptin administration downregulates the increased expression levels of genes related to oxidative stress and inflammation in the skeletal muscle of ob/ob mice. Mediat inflamm 2010. doi:10.1155/2010/784343
  • [17]Gülen Ş, Dinçer S: Effects of leptin on oxidative stress in healthy and Streptozotocin-induced diabetic rats. Mol Cell Biochem 2007, 302(1–2):59-65.
  • [18]World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Report of a WHO/IDF Consultation, 2006: 1-46.
  • [19]Anoop Misra A, Shrivastava U: Obesity and Dyslipidemia in South Asians. Nutrients 2013, 5(7):2708-33.
  • [20]BMI OC: Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. 1998.
  • [21]Yagi K: Lipid peroxides and human diseases. Chem Phys Lipids 1987, 45(2):337-51.
  • [22]Kakkar P, Das B, Viswanathan PN: A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984, 21(2):130-2.
  • [23]Rotruck J, Pope A, Ganther H, Swanson A, Hafeman D, Hoekstra W: Selenium: biochemical role as a component of glutathione peroxidase. Science 1973, 179(4073):588-90.
  • [24]Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R: Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 2003, 329(1–2):23-38.
  • [25]Hwa JJ, Fawzi AB, Graziano MP, Ghibaudi L, Williams P, Van Heek M, et al.: Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice. Am J Physiol 1997, 272(4):R1204-9.
  • [26]Segal K, Landt M, Klein S: Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 1996, 45(7):988-91.
  • [27]Solinas G: Leptin Signalling Coordinates Lipid Oxidation with Thermogenesis and Defence Against Oxidative Stress. Clin Exp Pharmacol Physiol 2010, 37(10):953-4.
  • [28]Kesavulu M, Rao BK, Giri R, Vijaya J, Subramanyam G, Apparao C: Lipid peroxidation and antioxidant enzyme status in Type 2 diabetics with coronary heart disease. Diabetes Res Clin Pract 2001, 53(1):33-9.
  • [29]Pandey KB, Mishra N, Rizvi SI: Protein oxidation biomarkers in plasma of type 2 diabetic patients. Clin Biochem 2010, 43(4):508-11.
  • [30]Yamagishi SI, Edelstein D, Du X-l, Kaneda Y, Guzmán M, Brownlee M. Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem. 2001;276(27):25096–100.
  • [31]DeFronzo RA, Ferrannini E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14(3):173-94.
  • [32]Balasubramaniyan V, Shukla R, Murugaiyan G, Bhonde RR, Nalini N: Mouse recombinant leptin protects human hepatoma HepG2 against apoptosis, TNF-alpha response andoxidative stress induced by the hepatotoxin-ethanol. Biochim Biophys Acta 2007, 1770(8):1136-44.
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