Leptin And Ghrelin – The New Old Players In Obesity And Depression

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The participation of the anorexigenic peptide leptin and the orexigenic peptide ghrelin in the pathogenesis of metabolic syndrome and obesity is well studied. In this review, we are taking a look at the structure, anatomical expression, regulation, receptors and physiological functions of these two neuropeptides. Leptin is produced almost exclusively in adipose tissue. It acts on the brain and is a key element in long-term regulation of energy balance. Leptin suppresses appetite and reduces body weight. Besides its central effects, important aspects of its action on peripheral tissues have been discovered recently: direct regulation of immune cells, pancreatic beta cells, adipocytes and muscle cells. Ghrelin is an endogenous ligand for the active form of the growth hormone receptor (GHS-R1a) and stimulates food intake and growth hormone secretion. We focus on the role of leptin and ghrelin in central nervous system neural mechanisms that are associated with depression. Studying new aspects of these two neuropeptides aims to expand our knowledge of the pathogenesis and therapeutic approaches to diseases with which they are associated: obesity, depression, type 2 diabetes, essential hypertension, and more.

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  • 1. Kojima M Hosoda H Date Y. Ghrelin is a growth-hormonereleasing acylated peptide from stomach. Nature.1999;402:656-60.

  • 2. Wren AM Small CJ Abbott CR Dhillo WS Seal LJ Cohen MA et al. Ghrelin causes hyperphagia and obesity in rats. Diabetes. 2001;50:2540-7.

  • 3. Smith-Kirwin SM O'Connor DM De Johnston J Lancey ED Hassink SG Funanage VL. Leptin expression in human mammary epithelial cells and breast milk. J Clin Endocrinol Metab. 1998;83(5):1810-3.

  • 4. Kojima M Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005;85(2):495-522.

  • 5. Paul RF Hassan M Nazar HS Gillani S Afzal N Qayyum I. Effect of body mass index on serum leptin levels. J Ayub Med Coll Abbottabad. 2011;23(3):40-43.

  • 6. Hellström L Wahrenberg H Hruska K Reynisdottir S Arner P. Mechanisms behind gender differences in circulating leptin levels. J Intern Med. 2000;247(4):457-62.

  • 7. Lee MJ Wang Y Ricci MR Sullivan S Russell CD Fried SK. Acute and chronic regulation of leptin synthesis storage and secretion by insulin and dexamethasone in human adipose tissue. Am J Physiol Endocrinol Metab. 2007;292(3):858-64.

  • 8. Scriba D Aprath-Husmann I Blum WF Hauner H. Catecholamines suppress leptin release from in vitro differentiated subcutaneous human adipocytes in primary culture via beta1- and beta2-adrenergic receptors. Eur J Endocrinol. 2000;143(3):439-45.

  • 9. Menendez C Baldelli R Camiña JP Escudero B Peino R Dieguez C et al. TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol. 2003;176(1):7-12.

  • 10. Gualillo O Lago F Garcia M Menendez C Senaris R Casanueva F et al. Prolactin stimulates leptin secretion by rat white adipose tissue. Endocrinology. 1999; 140(11):5149-53.

  • 11. Xiong Y Miyamoto N Shibata K Valasek MA Motoike T Kedzierski RM et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. PNAS. 2004;101(4):1045-50.

  • 12. Vatansever-Ozen S Tiryaki-Sonmez G Bugdayci G Ozen G. The effects of exercise on food intake and hunger: relationship with acylated ghrelin and leptin. Journal of Sports Science and Medicine. 201;10:283-91.

  • 13. Kageyama H Takenoya F Shiba K Shioda S. Neuronal circuits involving ghrelin in the hypothalamus-mediated regulation of feeding. Neuropeptides. 2010;44(2):133-8.

  • 14. Kamegai J Tamura H Shimizu T Ishii S Sugihara H Wakabayashi I. Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes. 2001;50(11):2438-43.

  • 15. Tartaglia LA Dembski M Weng X Deng N Culpepper J Devos R et al. Identification and expression cloning of a leptin receptor OB-R. Cell. 1995;83(7):1263-71.

  • 16. Münzberg H Björnholm M Bates SH Myers MG. Leptin receptor action and mechanisms of leptin resistance. CMLS Cellular and Molecular Life Sciences. 2005;62(6):642-652.

  • 17. Holst B Schwartz T. Constitutive ghrelin receptor activity as a signaling set-point in appetite regulation. Trends in Pharmacological Sciences. 2004;25(3):113-7.

  • 18. Holst B Cygankiewicz A Jensen TH Ankersen M Schwartz TW. High constitutive signaling of the ghrelin receptor-identification of a potent inverse agonist. Mol Endocrinol. 2003; 17(11):2201-10

  • 19. Attele AS Shi ZQ Yuan CS. Leptin gut and food intake. Biochem Pharmacol. 2002;63(9):1579-83.

  • 20. Lu XY. The leptin hypothesis of depression: a potential link between mood disorders and obesity? Curr Opin Pharmacol. 2007;7(6):648-52.

  • 21. Lawson EA Miller KK Blum JI Meenaghan E Misra M Eddy KT et al. Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum independent of body fat. Clin Endocrinol (Oxf). 2012;76(4):520-5.

  • 22. Deuschle M Blum WF Englaro P Schweiger U Weber B Pflaum CD et al. Plasma leptin in depressed patients and healthy controls. Hormone and Metabolic Research. 1996;28:714-7.

  • 23. Milaneschi Y Simonsick FM Penniux BW. Leptin abdominal obesity and onset of depression in older men and women. J Clin Psychiatry. 2012;73(9):1205-11.

  • 24. Phillips BG Kato M Narkiewicz K Choe I Somers VK. Increases in leptin levels sympathetic drive and weight gain in obstructive sleep apnea. Am J Physiol Heart Circ Physiol. 2000; 279(1):234-7.

  • 25. Sanner BM Kollhosser P Buechner N Zidek W Tepel M. Influence of treatment on leptin levels in patients with obstructive sleep apnoea. Eur Respir J. 2004;23(4):601-4.

  • 26. Brzechffa PR Jakimiuk AJ Agarwal SK Weitsman SR Buyalos RP Magoffin DA. Serum immunoreactive leptin concentrations in women with polycystic ovary syndrome. JCEM. 1996;81(11):4166-9.

  • 27. Lecke SB Mattei F Morsch DM Spritzer PM. Abdominal subcutaneous fat gene expression and circulating levels of leptin and adiponectin in polycystic ovary syndrome. Fertil Steril. 2011;95(6):2044-9.

  • 28. Rindi G Torsello A Locatelli V Solcia E. Ghrelin expression and actions: a novel peptide for an old cell type of the diffuse endocrine system. Exp Biol Med (Maywood). 2004;229(10):1007-16.

  • 29. Lutter M Sakata I Osborne-Lawrence S Rovinsky SA Anderson JG Jung S et al. The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci. 2008;11(7):752-3.

  • 30. Walker AK Rivera PD Wang Q Chuang JC Tran S Osborne-Lawrence S et al. The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis. Mol Psychiatry. 2014. doi: 10.1038/mp.2014.34.

  • 31. Chuang JC Perello M Sakata I Osborne-Lawrence S Savitt JM Lutter M et al. Ghrelin mediates stress-induced food-reward behavior in mice. J Clin Invest. 2011;121(7): 2684-92.

  • 32. Cummings DE Weigle DS Frayo RS Breen PA Ma MK Dellinger EP et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346:1623-30.

  • 33. Buchwald H Williams SE. Bariatric surgery worldwide 2003. Obes Surg. 2004;14:1157-64.

  • 34. Bizzarri C Rigamonti AE Luce A Cappa M Cella SG Berini J et al. Children with Prader–Willi syndrome exhibit more evident meal-induced responses in plasma ghrelin and peptide YY levels than obese and lean children. Eur J Endocrinol. 2010;162:499-505.

  • 35. Goldstone AP. Prader–Willi syndrome: advances in genetics pathophysiology and treatment. Trends Endocrinol Metab. 2004;15:12-20.

  • 36. Schüssler P Kluge M Yassouridis A Dresler M Uhr M Steiger A. Ghrelin Levels Increase After Pictures Showing Food. Obesity. 2012; 20(6):1212-7.

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