Skip to main content

Advertisement

SpringerLink
Log in

Effect of Intracerebroventricular Administration of Apelin-13 on the Hypothalamus–Pituitary–Thyroid Axis and Peripheral Uncoupling Proteins

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

Apelin, a ligand for G protein-coupled APJ receptor, is a peptide hormone. Although apelin and APJ receptors are determined in hypothalamus and thyroid gland its role in the hypothalamus–pituitary–thyroid (HPT) axis and mechanism of action on energy metabolism is not clear. This suggests that apelin may play a role in the HPT axis and energy metabolism. This study was designed to determine possible effects of centrally administered apelin-13 on the HPT axis and energy metabolism. A total of 40 adult male Sprague Dawley rats were divided into four groups (n = 10 each group). Intact rats served as control group while the sham group received vehicle of apelin. Apelin-13 was injected intracerebroventricularly at the doses of 1 and 10 nmol, for 7 days in the rats in the experimental group. At the end of the experimental protocol, animals were decapitated and brain, blood, white and brown adipose tissues samples were collected. There was no significant difference between the groups in terms of hypothalamic TRH mRNA levels. Serum TSH levels were significantly higher in all groups compared to the control group (p < 0.05). Serum fT3 and fT4 levels were significantly lower in apelin-13 administered groups (p < 0.05). Moreover, apelin-13 administered groups had lower levels of UCP1 mRNA in white and brown adipose tissues. UCP3 mRNA expression in muscle tissue was also lower in apelin-13 treated groups (p < 0.05). These results indicates that apelin-13 exhibits a decreasing effect on energy consumption through a mechanism involving the peripheral rather than central arms of the HPT axis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Amoo-Rajabi O, Moghimi A, Khazali H (2012) Effect of ICV injection of ghrelin and leptin on T3 and T4 plasma levels in rat. Physiol Pharmacol 16:70–78

    Google Scholar 

  • Attane C, Foussal C, Le Gonidec S et al (2012) Apelin treatment increases complete fatty acid oxidation, mitochondrial oxidative capacity, and biogenesis in muscle of insulin-resistant mice. Diabetes 61:310–320. doi:10.2337/db11-0100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bao H, Yang X, Huang Y, Qiu H, Huang G, Xiao H, Kuai J (2016) The neuroprotective effect of apelin-13 in a mouse model of intracerebral hemorrhage. Neurosci Lett 628:219–224. doi:10.1016/j.neulet.2016.06.046

    Article  PubMed  CAS  Google Scholar 

  • Bianco AC, Silva JE (1987) Intracellular conversion of thyroxine to triiodothyronine is required for the optimal thermogenic function of brown adipose tissue. J Clin Invest 79:295–300. doi:10.1172/JCI112798

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Boucher J, Masri B, Daviaud D et al (2005) Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology 146:1764–1771. doi:10.1210/en.2004-1427

    Article  PubMed  CAS  Google Scholar 

  • Castan-Laurell I, Dray C, Attane C, Duparc T, Knauf C, Valet P (2011) Apelin, diabetes, and obesity. Endocrine 40:1–9. doi:10.1007/s12020-011-9507-9

    Article  PubMed  CAS  Google Scholar 

  • Cusin I, Rouru J, Visser T, Burger AG, Rohner-Jeanrenaud F (2000) Involvement of thyroid hormones in the effect of intracerebroventricular leptin infusion on uncoupling protein-3 expression in rat muscle. Diabetes 49:1101–1105

    Article  CAS  Google Scholar 

  • de Lange P, Feola A, Ragni M et al (2007) Differential 3,5,3′-triiodothyronine-mediated regulation of uncoupling protein 3 transcription: role of fatty acids. Endocrinology 148:4064–4072. doi:10.1210/en.2007-0206

    Article  PubMed  CAS  Google Scholar 

  • Dray C, Debard C, Jager J et al (2010) Apelin and APJ regulation in adipose tissue and skeletal muscle of type 2 diabetic mice and humans. Am J Physiol Endocrinol Metab 298:E1161-1169. doi:10.1152/ajpendo.00598.2009

    Article  CAS  Google Scholar 

  • Erden Y, Tekin S, Kirbag S, al SS (2015) Mitochondrial uncoupling proteins in the brain: their structure, function and physiological roles [Beyindeki Mitokondriyal Eslesme Bozucu Proteinler: Yapýsý, Islevi ve Fizyolojik Rolleri]. Med Sci 4:2289–2307

    Article  Google Scholar 

  • Etem EO, Bal R, Akagac AE et al (2014) The effects of hydrated C(60) fullerene on gene expression profile of TRPM2 and TRPM7 in hyperhomocysteinemic mice. J Recept Signal Transduction 34:317–324. doi:10.3109/10799893.2014.896381

    Article  CAS  Google Scholar 

  • Fekete C, Lechan RM (2014) Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocr Rev 35:159–194. doi:10.1210/er.2013-1087

    Article  PubMed  CAS  Google Scholar 

  • Gurel A, Dogantekin A, Ozkan Y, Aydin S (2015) Serum apelin levels in patients with thyroid dysfunction. Int J Clin Exp Med 8:16394–16398

    PubMed  PubMed Central  CAS  Google Scholar 

  • Higuchi K, Masaki T, Gotoh K et al (2007) Apelin, an APJ receptor ligand, regulates body adiposity and favors the messenger ribonucleic acid expression of uncoupling proteins in mice. Endocrinology 148:2690–2697. doi:10.1210/en.2006-1270

    Article  PubMed  CAS  Google Scholar 

  • Hosoya M, Kawamata Y, Fukusumi S et al (2000) Molecular and functional characteristics of APJ. Tissue distribution of mRNA and interaction with the endogenous ligand apelin. J Biol Chem 275:21061–21067. doi:10.1074/jbc.M908417199

    Article  PubMed  CAS  Google Scholar 

  • Joly-Amado A, Cansell C, Denis RG, Delbes AS, Castel J, Martinez S, Luquet S (2014) The hypothalamic arcuate nucleus and the control of peripheral substrates. Best Pract Res Clin Endocrinol Metab 28:725–737. doi:10.1016/j.beem.2014.03.003

    Article  PubMed  Google Scholar 

  • Joseph-Bravo P, Jaimes-Hoy L, Charli JL (2015) Regulation of TRH neurons and energy homeostasis-related signals under stress. J Endocrinol 224:R139-159. doi:10.1530/JOE-14-0593

    Article  CAS  Google Scholar 

  • Khaksari M, Aboutaleb N, Nasirinezhad F, Vakili A, Madjd Z (2012) Apelin-13 protects the brain against ischemic reperfusion injury and cerebral edema in a transient model of focal cerebral ischemia. J Mol Neurosci 48:201–208. doi:10.1007/s12031-012-9808-3

    Article  PubMed  CAS  Google Scholar 

  • Krist J, Wieder K, Kloting N et al (2013) Effects of weight loss and exercise on apelin serum concentrations and adipose tissue expression in human obesity. Obes Facts 6:57–69. doi:10.1159/000348667

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lanni A, Moreno M, Lombardi A, Goglia F (2003) Thyroid hormone and uncoupling proteins. FEBS Lett 543:5–10

    Article  CAS  Google Scholar 

  • Lee DK, Cheng R, Nguyen T et al (2000) Characterization of apelin, the ligand for the APJ receptor. J Neurochem 74:34–41

    Article  CAS  Google Scholar 

  • Lee JY, Takahashi N, Yasubuchi M et al (2012) Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. Am J Physiol Cell Physiol 302:C463-472. doi:10.1152/ajpcell.00010.2011

    Article  CAS  Google Scholar 

  • Mahmoudi F, Mohsennezhad F, Khazali H, Ehtesham H (2011) The effect of central injection of ghrelin and bombesin on mean plasma thyroid hormones concentration. Iran J Pharm Res 10:627–632

    PubMed  PubMed Central  CAS  Google Scholar 

  • Masaki T, Yasuda T, Yoshimatsu H (2012) Apelin-13 microinjection into the paraventricular nucleus increased sympathetic nerve activity innervating brown adipose tissue in rats. Brain Res Bull 87:540–543. doi:10.1016/j.brainresbull.2012.02.004

    Article  PubMed  CAS  Google Scholar 

  • O’Carroll AM, Lolait SJ, Harris LE, Pope GR (2013) The apelin receptor APJ: journey from an orphan to a multifaceted regulator of homeostasis. J Endocrinol 219:R13-35. doi:10.1530/JOE-13-0227

    Article  PubMed  CAS  Google Scholar 

  • Ortiga-Carvalho TM, Chiamolera MI, Pazos-Moura CC, Wondisford FE (2016) Hypothalamus-pituitary-thyroid axis. Compr Physiol 6:1387–1428. doi:10.1002/cphy.c150027

    Article  PubMed  Google Scholar 

  • Pope GR, Roberts EM, Lolait SJ, O’Carroll AM (2012) Central and peripheral apelin receptor distribution in the mouse: species differences with rat. Peptides 33:139–148. doi:10.1016/j.peptides.2011.12.005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Queiroz MS, Shao Y, Ismail-Beigi F (2004) Effect of thyroid hormone on uncoupling protein-3 mRNA expression in rat heart and skeletal muscle. Thyroid 14:177–185. doi:10.1089/105072504773297849

    Article  PubMed  CAS  Google Scholar 

  • Rousset S, Alves-Guerra MC, Mozo J, Miroux B, Cassard-Doulcier AM, Bouillaud F, Ricquier D (2004) The biology of mitochondrial uncoupling proteins. Diabetes 53(Suppl 1):S130–S135

    Article  CAS  Google Scholar 

  • Sandal S, Tekin S, Yilmaz B (2014) Chronic intracerebroventricular apelin-13 infusion in rats increases daily food intake and body weight by reducing leptin levels. Acta Physiol 211:138–139

    Google Scholar 

  • Sandal S, Tekin S, Seker FB et al (2015) The effects of intracerebroventricular infusion of apelin-13 on reproductive function in male rats. Neurosci Lett 602:133–138. doi:10.1016/j.neulet.2015.06.059

    Article  PubMed  CAS  Google Scholar 

  • Taheri S, Murphy K, Cohen M et al (2002) The effects of centrally administered apelin-13 on food intake, water intake and pituitary hormone release in rats. Biochem Biophys Res Commun 291:1208–1212. doi:10.1006/bbrc.2002.6575

    Article  PubMed  CAS  Google Scholar 

  • Tatemoto K, Hosoya M, Habata Y et al (1998) Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 251:471–476. doi:10.1006/bbrc.1998.9489

    Article  PubMed  CAS  Google Scholar 

  • Tekin S, Erden Y, Etem E, Sandal S, Colak C (2014) Can Apelin-13 be a new actor in control of obesity? Acta Physiol 211:137–138

    Google Scholar 

  • Yamamoto T, Habata Y, Matsumoto Y et al (2011) Apelin-transgenic mice exhibit a resistance against diet-induced obesity by increasing vascular mass and mitochondrial biogenesis in skeletal muscle. Biochim Biophys Acta 1810:853–862. doi:10.1016/j.bbagen.2011.05.004

    Article  PubMed  CAS  Google Scholar 

  • Zorlu M, Kiskac M, Karatoprak C et al (2014) Assessment of serum apelin and lipocalin-2 levels in patients with subclinical hypothyroidism. Ann Endocrinol 75:10–14. doi:10.1016/j.ando.2013.12.001

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by Inonu University Scientific Research Projects Fund (Project # 2013/207).

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Science, Bartin University, Bartin, Turkey

    Yavuz Erden

  2. Department of Physiology, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey

    Suat Tekin, Umit Yilmaz & Suleyman Sandal

  3. Department of Public Health, Faculty of Medicine, Inonu University, Malatya, Turkey

    Cigdem Tekin

  4. Department of Biochemistry, Faculty of Medicine, Inonu University, Malatya, Turkey

    Fatma Ozyalin

  5. Department of Medical Biology, Faculty of Medicine, Fırat University, Elazig, Turkey

    Ebru Etem Onalan

  6. Department of Medical Biology and Genetics, Faculty of Medicine, Inonu University, Malatya, Turkey

    Yilmaz Cigremis

  7. Department of Biostatistics and Medical Informatics, Faculty of Medicine, Inonu University, Malatya, Turkey

    Cemil Colak

Authors
  1. Yavuz Erden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suat Tekin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cigdem Tekin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fatma Ozyalin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Umit Yilmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ebru Etem Onalan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yilmaz Cigremis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cemil Colak
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Suleyman Sandal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suleyman Sandal.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable institutional and national guidelines for the care and use of animals were followed. In this study, protocols for animal experiment were approved by the institutional animal ethical committee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erden, Y., Tekin, S., Tekin, C. et al. Effect of Intracerebroventricular Administration of Apelin-13 on the Hypothalamus–Pituitary–Thyroid Axis and Peripheral Uncoupling Proteins. Int J Pept Res Ther 24, 511–517 (2018). https://doi.org/10.1007/s10989-017-9638-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-017-9638-9

Keywords

Search

Navigation