Skip to main content

Advertisement

SpringerLink
Log in

An Intraperitoneal Treatment with Calcitonin Gene-Related Peptide (CGRP) Regulates Appetite, Energy Intake/Expenditure, and Metabolism

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide expressed both centrally and peripherally. CGRP has been shown to be involved in arteriolar dilation, cardiovascular regulation, pain transmission, migraine, and gastrointestinal physiology. Our current research is aimed at analyzing CGRP’s impact on appetite/satiety, body metabolism, and energy homeostasis. Our study investigated the effects of a single-dose intraperitoneal (IP) treatment with CGRP on food and water consumption, energy expenditure, physical activity, respirometry, and a panel of plasma metabolic hormones in C57Bl/6 wild-type (WT) mice. After a CGRP IP injection at a dose of 2 nmol (10 μM CGRP in 200 μl of saline), a significant reduction in food intake and metabolic parameters as RQ, VCO2, and VO2 was observed. CGRP-injected mice had also significantly lower total energy expenditure (TEE) with no changes in activity levels compared to vehicle-injected controls. CGRP treatment in mice induced significantly lower plasma levels of glucagon and leptin but higher levels of amylin. Our data show that a single dose of CGRP peptide significantly decreased food consumption and altered calorimetric parameters and plasma metabolic hormone levels, thus confirming that CGRP plays a pivotal role in the regulation of appetite and metabolism. Future studies are necessary to analyze CGRP’s long-term impact on body metabolism and its potential effects on appetite, obesity, and metabolic disorders.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adult Obesity Facts Centers for Disease Control and Prevention (2018) https://www.cdc.gov/obesity/data/adult.html

  • Bachmanow AA, Reed DR, Beauchamp GK, Tordoff MG (2002) Food intake, water intake, and drinking spout side preference of 28 mouse strains. Behav Genet 32:435–443

    Article  Google Scholar 

  • Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I (1985) Calcitonin gene-related peptide is a potent vasodilator. Nature 313:3–9

    Article  Google Scholar 

  • Carter ME, Soden ME, Zweifel LS, Palmiter RD (2013) Genetic identification of a neural circuit that suppresses appetite. Nature 503:111–114

    Article  CAS  Google Scholar 

  • Cline MA, Calchary WA, Nandar W (2009) Effect of calcitonin gene-related peptide (CGRP) on avian appetite-related processes. Behav Brain Res 196:242–247

    Article  CAS  Google Scholar 

  • Cottrell GS, Roosterman D, Marvizon JC, Song B, Wick E, Pikios S, Wong H, Berthelier C, Tang Y, Sernini C, Bunnett NW, Grady EF (2005) Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat. J Comp Neurol 490:239–255

    Article  CAS  Google Scholar 

  • Danaher RN, Loomes KM, Leonard BL, Whiting L, Hay DL, Xu LY, Kraegen EW, Phillips AR, Cooper GJ (2008) Evidence that alpha-calcitonin gene-related peptide is a neurohormone that controls systemic lipid availability and utilization. Endocrinology 149:154–160

    Article  CAS  Google Scholar 

  • Dhillo WS, Small CJ, Jethwa PH, Russell SH, Gardiner JV, Bewick GA, Seth A, Murphy KG, Ghatei MA, Bloom SR (2003) Paraventricular nucleus administration of calcitonin gene-related peptide inhibits food intake and stimulates the hypothalamo-pituitary-adrenal axis. Endocrinology 144:1420–1425

    Article  CAS  Google Scholar 

  • Edvinsson L, Tfelt-Hansen P (2008) The blood-brain barrier in migraine treatment. Cephalalgia: An International Journal of Headache 28:1245–1258

    Article  CAS  Google Scholar 

  • Edvinsson L, Nilsson E, Jansen-Olsen I (2007) Inhibitory effect of BIBN4096BS, CGRP8–37, a CGRP antibody and an RNA-Spiegelmer on CGRP induced vasodilatation in the perfused and non-perfused rat middle cerebral artery. Br J Pharmacol 150:633–640

    Article  CAS  Google Scholar 

  • Greenwood HC, Bloom SR, Murphy KG (2011) Peptides and their potential role in the treatment of diabetes and obesity. Society for Biomedical Diabetes Research

  • Hansen MB (2003) Neurohumoral control of gastrointestinal motility. Physiol Res 52:1–30

    CAS  PubMed  Google Scholar 

  • Hermansen K, Ahrén B (1990) Dual effects of calcitonin gene-related peptide on insulin secretion in the perfused dog pancreas. Regul Pept 27:149–157

    Article  CAS  Google Scholar 

  • Hüttemeier PC, Ritter EF, Benveniste H (1993) Calcitonin gene-related peptide mediates hypotension and tachycardia in endotoxic rats. Am J Phys 265:767–769

    Google Scholar 

  • Juhasz G, Zsombok T, Modos EA, Olajos S, Jakab B, Nemeth J, Szolcsanyi J, Vitrai J, Bagdy G (2003) NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release. International Association for the Study of. Pain 106:461–470

    Article  CAS  Google Scholar 

  • Kaiser EA, Russo AF (2013) CGRP and migraine: could PACAP play a role too? Neuropeptides 47:451–461

    Article  CAS  Google Scholar 

  • Kawashima K, Ishihara S, Karim Rumi MA, Moriyama N, Kazumori H, Suetsugu H, Sato H, Fukuda R, Adachi K, Shibata M, Onodera S, Chiba T, Kinoshita Y (2002) Localization of calcitonin gene-related peptide receptors in rat gastric mucosa. Peptides 23:955–966

    Article  CAS  Google Scholar 

  • Kraenzlin ME, Ch’ng JLC, Mulderry PK, Ghatei MA, Bloom SR (1985) Infusion of a novel peptide, calcitonin gene-related peptide (CGRP) in man. Pharmacokinetics and effects on gastric acid secretion and on gastrointestinal hormones. Regul Pept 10:189–197

    Article  CAS  Google Scholar 

  • Krahn DD, Gosnell BA, Levine AS, Morley JE (1984) Effects of calcitonin gene-related peptide on food intake. Peptides 5:861–864

    Article  CAS  Google Scholar 

  • Kreutter DK, Orena SJ, Torchia AJ, Contillo LG, Andrews GC, Stevenson RW (1993) Amylin and CGRP induce insulin resistance via a receptor distinct from cAMP-coupled CGRP receptor. Am J Phys 264:606–613

    Google Scholar 

  • Leighton B, Cooper GJ (1988) Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature 335:632–635

    Article  CAS  Google Scholar 

  • Lennerz JK, Rühle V, Ceppa EP, Neuhuber WL, Bunnett NW, Grady EF, Messlinger K (2008) Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: differences between peripheral and central CGRP receptor distribution. J Comp Neurol 507:1277–1299

    Article  CAS  Google Scholar 

  • Lighton JRB (2008) Measuring metabolic rates: a manual for scientists, 1st edn. Oxford University Press, New York

    Book  Google Scholar 

  • Liu T, Kamiyoshi A, Sakurai T, Ichikawa-Shindo Y, Kawate H, Yang L, Tanaka M, Xian X, Imai A, Zhai L, Hirabayashi K, Dai K, Tanimura K, Liu T, Cui N, Igarashi K, Yamauchi A, Shindo T (2017) Endogenous calcitonin gene-related peptide regulates lipid metabolism and energy homeostasis in male mice. Endocrinology 158:1194–1206

    Article  Google Scholar 

  • Lutz TA, Rossi R, Althaus J, Del Prete E, Scharrer E (1998) Amylin reduces food intake more potently than calcitonin gene-related peptide (CGRP) when injected into the lateral brain ventricle in rats. Peptides 19:1533–1540

    Article  CAS  Google Scholar 

  • Martinez V, Taché Y (2006) Calcitonin gene-related peptide and gastrointestinal function. Handbook of Biologically Active Peptides 138:1005–1011

    Article  Google Scholar 

  • Morley JE, Farr SA, Flood JF (1996) Peripherally administered calcitonin gene-related peptide decreases food intake in mice. Peptides 17:511–516

    Article  CAS  Google Scholar 

  • Nilsson C, Hansen TK, Rosenquist C, Hartmann B, Kodra JT, Lau JF, Clausen TR, Raun K, Sams A (2016) Long acting analogue of the calcitonin gene-related peptide induces positive metabolic effects and secretion of the glucagon-like peptide-1. Eur J Pharmacol 773:24–31

    Article  CAS  Google Scholar 

  • Pappas T, Debas HT, Walsh JH, Rivier J, Taché Y (1986) Calcitonin gene-related peptide-induced selective inhibition of gastric acid secretion in dogs. Am J Phys 250:127–133

    Google Scholar 

  • Parsons AM, Seybold VS (1997) Calcitonin gene-related peptide induces the formation of second messengers in primary cultures of neonatal rat spinal cord. Synapse 26:235–242

    Article  CAS  Google Scholar 

  • Pettersson M, Ahrén B (1988) Insulin and glucagon secretion in rats: effects of calcitonin gene-related peptide. Regul Pept 23:37–50

    Article  CAS  Google Scholar 

  • Plaisancié P, Bernard C, Chayvialle JA, Cuber JC (2009) Release of peptide YY by neurotransmitters and gut hormones in the isolated, Vascularly Perfused Rat Colon. Scandinavian Journal of Gastroenterology 30:568–574

  • Raybould HE, Kolve E, Taché Y (1988) Central nervous system action of calcitonin gene-related peptide to inhibit gastric emptying in the conscious rat. Peptides 9:735–738

    Article  CAS  Google Scholar 

  • Rossetti L, Farrace S, Choi SB, Giaccari A, Sloan L, Frontoni S, Katz MS (1993) Multiple metabolic effects of CGRP in conscious rats: role of glycogen synthase and phosphorylase. Am J Physiol 264:E1–E10

    CAS  PubMed  Google Scholar 

  • Russell FA, King R, Smillie SJ, Kodji X, Brain SD (2014) Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev 94:1099–1142

    Article  CAS  Google Scholar 

  • Shahbazi F, Karila P, Olsson C, Holmgren S, Conlon JM, Jensen J (1998) Primary structure, distribution, and effects on motility of CGRP in the intestine of the cod Gadus morhua. Am J Phys 275:19–28

    Google Scholar 

  • Sun JY, Jing MY, Wang JF, Weng XY (2010) The approach to the mechanism of calcitonin gene-related peptide-inducing inhibition of food intake. J Anim Physiol Anim Nutr 94:552–560

    Article  CAS  Google Scholar 

  • Taché Y, Raybould H, Wei JY (1991) Central and peripheral actions of calcitonin gene-related peptide on gastric secretory and motor function. Adv Exp Med Biol 298:183–198

    Article  Google Scholar 

  • Tanaka H, Kashiwagi R, Koizumi T (2013) Inhibition of calcitonin gene-related peptide (CGRP) has the potential to extend first-phase insulin secretion. Exp Clin Endocrinol Diabetes 121:280–285

    Article  CAS  Google Scholar 

  • Vu JP, Luong L, Parsons WF, Oh S, Sanford D, Gabalski A, Lighton JRB, Pisegna JR, Germano PM (2017) Long-term intake of a high-protein diet affects body phenotype, metabolism, and Plasma Hormones in Mice. The Journal of Nutrition 147:2243–2251

    Article  CAS  Google Scholar 

  • Walker CS, Li X, Whiting L, Glyn-Jones S, Zhang S, Hickey AJ, Sewell MA, Ruggiero K, Phillips ARJ, Kraegen EW, Hay DL, Cooper GJS, Loomes KM (2010) Mice lacking the neuropeptide α-calcitonin gene-related peptide are protected against diet-induced obesity. Endocrinology 151:4257–4269

    Article  CAS  Google Scholar 

  • Weir JBDV (1949) New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol 109:1–9

    Article  Google Scholar 

  • Wimalawansa SJ (1990) Effects of in vivo stimulation on molecular forms of circulatory calcitonin and calcitonin gene-related peptide in man. Mol Cell Endocrinol 71:13–19

    Article  CAS  Google Scholar 

  • Wimalawansa SJ (1996) Calcitonin gene-related peptide and its receptors: molecular genetics, physiology, pathophysiology, and therapeutic potentials. Endocrinology Reviews 17:533–585

    Article  CAS  Google Scholar 

  • Woods SC, Seeley RJ, Porte DJ, Schwartz MW (1998) Signals that regulate food intake and energy homeostasis. Science 280:1378–1383

    Article  CAS  Google Scholar 

  • Yamaguchi A, Chiba T, Morishita T, Nakamura A, Inui T, Yamatani T, Kadowaki S, Chihara K, Fukase M, Fujita T (1990) Calcitonin gene-related peptide and induction of hyperglycemia in conscious rats in vivo. Diabetes 39:168–174

    Article  CAS  Google Scholar 

  • Yarwood RE, Imlach WL, Lieu T, Veldhuis NA, Jensen DD, Klein HC, Aurelio L, Cai Z, Christie MJ, Poole DP, Porter CJH, McLean P, Hicks GA, Geppetti P, Halls ML, Canals M, Bunnett NW (2017) Endosomal signaling of the receptor for calcitonin gene-related peptide mediates pain transmission. Proc Natl Acad Sci U S A 114:12309–12314

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CURE/Digestive Diseases Research Center, Department of Medicine at the David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Daniel Sanford, Leon Luong, Arielle Gabalski, Suwan Oh, John P. Vu, Joseph R. Pisegna & Patrizia Germano

  2. Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Daniel Sanford, Leon Luong, Arielle Gabalski, Suwan Oh, John P. Vu & Joseph R. Pisegna

  3. Research Service Department, Veterans Affairs Greater Los Angeles Healthcare System, Bldg.115 Rm 313, Los Angeles, CA, USA

    Daniel Sanford, Leon Luong, Arielle Gabalski, Suwan Oh, John P. Vu, Joseph R. Pisegna & Patrizia Germano

  4. Division of Digestive Diseases, David Geffen School of Medicine Los Angeles, Los Angeles, CA, USA

    Joseph R. Pisegna

  5. Division of Pulmonary and Critical Care, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Patrizia Germano

Authors
  1. Daniel Sanford
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leon Luong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arielle Gabalski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suwan Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John P. Vu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joseph R. Pisegna
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Patrizia Germano
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.S., J.P.V., J.R.P., and P.G. conception and design of research; D.S., J.P.V., L.L., S.O., A.G., J.R.P., and P.G. performed experiments, D.S., J.P.V., L.L., S.O., A.G., J.R.P., and P.G. analyzed data; D.S., J.P.V., L.L., S.O., A.G., J.R.P., and P.G. interpreted results of experiments; D.S., J.P.V., J.R.P., and P.G. prepared figures; D.S., J.P.V., J.R.P., and P.G. drafted manuscript; D.S., J.P.V., L.L., S.O., A.G., J.R.P., and P.G. edited and revised manuscript; D.S., J.P.V., L.L., S.O., A.G., J.R.P., and P.G. approved final version of manuscript.

Corresponding author

Correspondence to Patrizia Germano.

Ethics declarations

Grants

VA Merit Review I01RX000873 (Germano, P).

VA ShEEP IS1BX003075 (Germano, P).

VA ShEEP IS1BX003553 (Germano, P).

NIH NIDDK P30 NIH DK41301.

NIH NIDDK U01 CSCPDPC -CCs -RFA-DK-14-027.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sanford, D., Luong, L., Gabalski, A. et al. An Intraperitoneal Treatment with Calcitonin Gene-Related Peptide (CGRP) Regulates Appetite, Energy Intake/Expenditure, and Metabolism. J Mol Neurosci 67, 28–37 (2019). https://doi.org/10.1007/s12031-018-1202-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-018-1202-3

Keywords

Search

Navigation