The effect of adropin on lipid and glucose metabolism in rats with hyperlipidemia

Document Type : Original Article


1 University of Dumlupınar, Faculty of Medicine, Department of Physiology, Kütahya, Turkey

2 University of Dumlupınar, Faculty of Medicine, Department of Biochemistry, Kütahya, Turkey

3 University of Dumlupınar, Faculty of Medicine, Experimental Animal Research Center, Kütahya, Turkey

4 University of Dumlupınar, Faculty of Arts and Sciences, Department of Biochemistry, Kütahya, Turkey


Objective(s):The aim of this study was to evaluate, for the first time, whether the effects of low-dose adropin administration is effective in rats with hyperlipidemia.
Materials and Methods: Twenty one Wistar albino female rats were randomly divided into 3 groups and fed with high-fat diet for 4 weeks to establish the hyperlipidemia model. Meanwhile, adropin was administrated intraperitonealy (2.1 μg/kg/day), once a day for continuous 10 days. Then, body weights and serum biochemical parameters, adropin, insulin and blood glucose levels were determined. Additionally, in liver tissue, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) mRNA gene expressions were evaluated by RT-PCR.
Results:The results showed that intraperitoneal administration of adropin to hyperlipidemic rats for 10 days were extremely effective in decreasing the levels of serum triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamil transferase (GGT) and increasing the levels of high density lipoprotein cholesterol (HDL-C). It could decrease mRNA expressions of pro-inflammatory cytokines TNF-α and IL-6 via regulating the expressions of iNOS. In addition, treatment with adropin showed a significant reduction in blood glucose, serum insulin levels, HbA1c (%), and HOMA-IR, and increase in serum adropin levels.
Conclusion: Adropin may ameliorate lipid metabolism, reduce insulin resistance, and inhibit hepatocytes inflammation. Thus, adropin had significant therapeutic benefits and could be suggested as a potential candidate agent against hyperlipidemia.


1. Suk HY, Zhou C, Yang TT, Zhu H, Yu RY, Olabisi O, Yang X, Brancho D, Kim JY, Scherer PE, Frank PG, Lisanti MP, Calvert JW, Lefer DJ, Molkentin JD, Ghigo A, Hirsch E, Jin J, Chow CW.Ablation of calcineurin Aβ reveals hyperlipidemia and signaling cross-talks with phosphodiesterases. J Biol Chem. 2013; 288:3477–3488.
2. Pöss J, Custodis F, Werner C, Weingärtner O, Böhm M, Laufs U. Cardiovascular disease and dyslipidemia: beyond LDL. Curr Pharm Des. 2011; 17:861–870.
3. Vaziri ND, Norris K. Lipid disorders and their relevance to outcomes in chronic kidney disease. Blood Purif. 2011; 31:189–196.
4. Lu ZL, Xu ZM, Kou WR, Zhao SP. Advance in basic and clinical research of Xuezhikang capsule. Chin J Integr Med. 2006; 12:85–93
5. Priego T, Sa´nchezJ, Pico´C, Palou A. Sex-differential expression of metabolism- related genes in response to a high-fat diet. Obesity.2008; 16:819–826.
6. Taraschenko OD, Maisonneuve IM, Glick SD. Sex differences in high fat-induced obesity in rats:              effects of 18-methoxycoronaridine. Physiol Behav. 2011; 103:308-314.
7. Fernandez ML. The metabolic syndrome. Nutr Rev 2007; 65:S30–S34.
8. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism.2013; 62, 457–478.
9. Kumar KG, Trevaskis JL, Lam DD, Sutton GM, Koza RA, Chouljenko VN, Kousoulas KG, Rogers PM, Kesterson RA, Thearle M, Ferrante AW Jr, Mynatt RL, Burris TP, Dong JZ, Halem HA, Culler MD, Heisler LK, Stephens JM, Butler AA.Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab. 2008; 8: 468–481.
10. Aydin S, Kuloglu T, Aydin S, Eren MN, Yilmaz M, Kalayci M, Sahin I, Kocaman N, Citil C, Kendir Y. Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes. Mol Cell Biochem. 2013; 380:73–81.
11. Ai J, Wang N, Du J, Yang M, Liu P, Du Z. Establishment of type 2 diabetic animal model in in Wistar rats. Chin Pharmacol Bull 2004; 20:1309–1312.
12. Yang R, Guo P, Song X, Liu F, Gao N. Hyperlipidemic guinea pig model: mechanisms of triglyceride metabolism disorder and comparison to rat. Biol Pharm Bull. 2011; 34:1046-1051.
13. Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta M, Al-Omran M, Teoh H, Verma S. Adropin is a novel regulator of endothelial function. Circulation. 2010; 14:185-192.
14. Ibrahim MA, Islam MS. Anti-diabetic effects of the acetone fraction of Senna singueana stem bark in a type 2 diabetes rat model. J Ethnopharmacol. 2014; 28; 153:392-409.
15. Bagdade JD, Helve E, Taskinen MR. Effect of continuous insulin infusion therapy lipoprotein surface and core lipid composition in IDDM. Metabolism. 1991; 40:445–449.
16. Onody A, Csonka C, Giricz Z, Ferdinandy P. Hyperlipidemia induced by a cholesterol-rich diet leads to enhanced peroxynitrate formation in rat hearts. Cardiovasc Res.2003; 58:663–670.
17. Shew WH, Jeng CY, Lee WJ, Lin SY, Pei D, Chen YT. Simvastatin treatment in postprandial hypertri-glyceridemia in type 2 diabetes mellitus patients with combined hyperlipidemia. Metabolism. 2001; 50:355-359.
18. Miao H, Chen H, Pei S, Bai X, Vaziri ND, Zhao YY.
Plasma lipidomics reveal profound perturbation of glycerophospholipids, fatty acids, and sphingolipids in diet-induced hyperlipidemia. Chem Biol Interact. 2015; 25:79-87.
19. Butler AA, Tam CS, Stanhope KL, Wolfe BM, Ali MR, O'Keeffe M, St-Onge MP, Ravussin E, Havel PJ. Low circulating adropin concentrations with obesity and aging correlate with risk factors for metabolic disease and increase after gastric bypass surgery in humans. J Clin Endocrinol Metab. 2012; 97:3783-3791.
20. Yildirim B, Celik O, Aydin S. Adropin: a key component and potential gatekeeper of metabolic disturbances in policystic ovarian syndrome. Clin Exp Obstet Gynecol. 2014; 41:310-312.
21. Kumar KG, Zhang J, Gao S, Rossi J, McGuinness OP, Halem HH, Culler MD, Mynatt RL, Butler AA.Adropin deficiency is associated with increased adiposity and insulin resistance. Obesity (Silver Spring).2012; 20:1394–1402.
22. Eu CH, Lim WY, Ton SH, bin Abdul Kadir K. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats. Lipids Health Dis. 2010; 29; 9:81.
23. Gao S, McMillan RP, Zhu Q, Lopaschuk GD, Hulver MW, Butler AA. Therapeutic effects of adropin on glucose tolerance and substrate utilization in diet-induced obese mice with insulin resistance. Mol Metab. 2015; 17; 4:310-324.
24. Aydin S. Three new players in energy regulation: preptin, adropin and irisin. Peptides. 2014; 56: 94-110.
25. Abbas AM, Sakr HF. Simvastatin and vitamin E effects on cardiac and hepatic oxidative stress in rats fed on high fat diet. J Physiol Biochem. 2013; 69:737-750.
26. Ding M, Si D, Zhang W, Feng Z, He M, Yang P. Red yeast rice repairs kidney damage and reduces inflammatory transcription factors in rat models of hyperlipidemia. Exp Ther Med. 2014; 8:1737-1744.
27. Wang WQ, Zhang HF, Gao GX, Baı QX, Lı R, Wang XM. Adiponectin Inhibits Hyperlipidemia-Induced Platelet Aggregation via Attenuating Oxidative/Nitrative Stress. Physiol Res. 2011; 60: 347-354.
28. Kuloglu T, Aydin S. Immunohistochemical expressions of adropin and inducible nitric oxide synthase in renal tissues of rats with streptozotocin-induced experimental diabetes. Biotech Histochem. 2014; 89:104-110.