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Published in: Comparative Clinical Pathology 5/2017

01-09-2017 | Original Article

The central effect of 3-iodothyronamine on brain neuropeptides in mice

Authors: N. Kazemipour, N. Eskandarzade, R. Beigi, S. Nazifi

Published in: Comparative Clinical Pathology | Issue 5/2017

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Abstract

3-Iodothyronamine (T1AM) is an endogenous metabolite of thyroid hormone with noticeable metabolic and neurological effects. Alteration of feeding behaviour by this compound was different at various doses in experimental models and it is not clear whether this effect is partially accounted by changes in neuropeptide secretion. In this study, we attempted to find out whether chronic low dose 3-iodothyronamine treatment could modulate some food intake regulatory neuropeptides such as leptin, ghrelin, and galanin in mice brain. Eighteen male mice were divided randomly into control (n = 8) and treatment (n = 10) groups. The experimental procedure was applied for 7 days during which treatment group received T1AM (i.p) whereas the control group received DMSO and normal saline. The brain was analyzed for leptin, ghrelin, and galanin concentrations. There were significant differences in leptin concentration (1.75 ± 0.05 versus 2.9 ± 0.07 ng/ml) and ghrelin concentration (8.4 ± 0.35 versus 5 ± 0.08 ng/ml) between control and treatment groups (P < 0.05). There was no significant difference in galanin concentration (745.87 ± 34.91 ng/l) in control group compared with the treatment group (698.05 ± 66.88 ng/l). Interestingly, the treatment group mice lost weight (~1 g) whereas non-significant increase in weight mean was seen in control group before (day 1) and after the procedure (day 8). Clearly, further works in this area will be required to delineate the central role of T1AM, but based on our findings described here, we propose that some of peripheral metabolic effects of this compound may be accomplished by brain peptide regulation.
Literature
go back to reference Alpergin E, Bolandnazar Z, Sabatini M, Rogowski M, Chiellini G, Zucchi R, Assadi-Porter F (2017) Metabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3-iodothyronamine. Physiol Rep 5:e13097CrossRef Alpergin E, Bolandnazar Z, Sabatini M, Rogowski M, Chiellini G, Zucchi R, Assadi-Porter F (2017) Metabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3-iodothyronamine. Physiol Rep 5:e13097CrossRef
go back to reference Banks WA, Tschop M, Robinson SM, Heiman ML (2002) Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther 302:822–827CrossRefPubMed Banks WA, Tschop M, Robinson SM, Heiman ML (2002) Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther 302:822–827CrossRefPubMed
go back to reference Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci 98:8966–8971CrossRefPubMedPubMedCentral Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (2001) Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci 98:8966–8971CrossRefPubMedPubMedCentral
go back to reference Baranowska B, Chmielowska M, Wolinska-Witort E, Roguski K, Wasilewska-Dziubinska E (2001) The relationship between neuropeptides and hormones in starvation. Neuroendocrinol Lett 22:349–355PubMed Baranowska B, Chmielowska M, Wolinska-Witort E, Roguski K, Wasilewska-Dziubinska E (2001) The relationship between neuropeptides and hormones in starvation. Neuroendocrinol Lett 22:349–355PubMed
go back to reference Cai H, Haubensak W, Anthony TE, Anderson DJ (2014) Central amygdala PKC-delta(+) neurons mediate the influence of multiple anorexigenic signals. Nat Neurosci 17:1240–1248CrossRefPubMedPubMedCentral Cai H, Haubensak W, Anthony TE, Anderson DJ (2014) Central amygdala PKC-delta(+) neurons mediate the influence of multiple anorexigenic signals. Nat Neurosci 17:1240–1248CrossRefPubMedPubMedCentral
go back to reference Chiellini G, Frascarelli S, Ghelardoni S, Carnicelli V, Tobias SC, DeBarber A, Brogioni S, Ronca-Testoni S, Cerbai E, Grandy DK, Scanlan TS, Zucchi R (2007) Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function. FASEB J 21:1597–1608CrossRefPubMed Chiellini G, Frascarelli S, Ghelardoni S, Carnicelli V, Tobias SC, DeBarber A, Brogioni S, Ronca-Testoni S, Cerbai E, Grandy DK, Scanlan TS, Zucchi R (2007) Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function. FASEB J 21:1597–1608CrossRefPubMed
go back to reference Dhillo WS, Bewick GA, White NE, Gardiner JV, Thompson EL, Bataveljic A, Murphy KG, Roy D, Patel NA, Scutt JN, Armstrong A, Ghatei MA, Bloom SR (2009) The thyroid hormone derivative 3-iodothyronamine increases food intake in rodents. Diabetes Obes Metab 11:251–260CrossRefPubMed Dhillo WS, Bewick GA, White NE, Gardiner JV, Thompson EL, Bataveljic A, Murphy KG, Roy D, Patel NA, Scutt JN, Armstrong A, Ghatei MA, Bloom SR (2009) The thyroid hormone derivative 3-iodothyronamine increases food intake in rodents. Diabetes Obes Metab 11:251–260CrossRefPubMed
go back to reference Fry M, Ferguson AV (2007) The sensory circumventricular organs: brain targets for circulating signals controlling ingestive behavior. Physiol Behavior 91:413–423CrossRef Fry M, Ferguson AV (2007) The sensory circumventricular organs: brain targets for circulating signals controlling ingestive behavior. Physiol Behavior 91:413–423CrossRef
go back to reference Hakansson ML, Brown H, Ghilardi N, Skoda RC, Meister B (1998) Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci 18:559–572PubMed Hakansson ML, Brown H, Ghilardi N, Skoda RC, Meister B (1998) Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus. J Neurosci 18:559–572PubMed
go back to reference Haviland JA, Reiland H, Butz DE, Tonelli M, Porter WP, Zucchi R, Scanlan TS, Chiellini G, Assadi-Porter FM (2013) NMR based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1AM treatment. Obesity 21:2538–2544CrossRefPubMedPubMedCentral Haviland JA, Reiland H, Butz DE, Tonelli M, Porter WP, Zucchi R, Scanlan TS, Chiellini G, Assadi-Porter FM (2013) NMR based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1AM treatment. Obesity 21:2538–2544CrossRefPubMedPubMedCentral
go back to reference Hettinger BD, Schuff K, Marks D, Scanlan TS (2010) 3-iodothyronamine (T1AM) causes weight loss in mice via reduction in food consumption [abstract], in 14th International Thyroid Congress OC-141, Paris Hettinger BD, Schuff K, Marks D, Scanlan TS (2010) 3-iodothyronamine (T1AM) causes weight loss in mice via reduction in food consumption [abstract], in 14th International Thyroid Congress OC-141, Paris
go back to reference Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB (2004) Ghrelin—a hormone with multiple functions. Front Neuroendocrinol 25:27–68CrossRefPubMed Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB (2004) Ghrelin—a hormone with multiple functions. Front Neuroendocrinol 25:27–68CrossRefPubMed
go back to reference Manni ME, DeSiena G, Saba A, Marchini M, Dicembrini I, Bigagli E, Cinci L, Lodovici M, Chiellini G, Zucchi R, Raimondi L (2012) 3-Iodothyronamine: a modulator of the hypothalamus-pancreas-thyroid axes in mice. Br J Pharmacol 166:650–658CrossRefPubMedPubMedCentral Manni ME, DeSiena G, Saba A, Marchini M, Dicembrini I, Bigagli E, Cinci L, Lodovici M, Chiellini G, Zucchi R, Raimondi L (2012) 3-Iodothyronamine: a modulator of the hypothalamus-pancreas-thyroid axes in mice. Br J Pharmacol 166:650–658CrossRefPubMedPubMedCentral
go back to reference Laque A, Zhang Y, Gettys S, Nguyen TA, Bui K, Morrison CD, Munzberg H (2013) Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action. Am J Physiol Endocrinol Metab 304:E999–E1011CrossRefPubMedPubMedCentral Laque A, Zhang Y, Gettys S, Nguyen TA, Bui K, Morrison CD, Munzberg H (2013) Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action. Am J Physiol Endocrinol Metab 304:E999–E1011CrossRefPubMedPubMedCentral
go back to reference Panas HN, Lynch LJ, Vallender EJ, Xie Z, Chen GL, Lynn SK, Scanlan TS, Miller GM (2010) Normal thermoregulatory responses to 3-iodothyronamine, trace amines and amphetamine-like psychostimulants in trace amine associated receptor 1 knockout mice. J Neurosci Res 88:1962–1969PubMedPubMedCentral Panas HN, Lynch LJ, Vallender EJ, Xie Z, Chen GL, Lynn SK, Scanlan TS, Miller GM (2010) Normal thermoregulatory responses to 3-iodothyronamine, trace amines and amphetamine-like psychostimulants in trace amine associated receptor 1 knockout mice. J Neurosci Res 88:1962–1969PubMedPubMedCentral
go back to reference Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK (2004) 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med 10:638–642CrossRefPubMed Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK (2004) 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med 10:638–642CrossRefPubMed
go back to reference Tang G, Wang Y, Park S, Bajpayee NS, Vi D, Nagaoka Y, Birnbaumer L (2012) Jiang M (2012) Go2Gprotein mediates galanin inhibitory effects on insulin release from pancreatic 훽 cells. Proc Natl Acad Sci U S A 109:2636–2641CrossRefPubMedPubMedCentral Tang G, Wang Y, Park S, Bajpayee NS, Vi D, Nagaoka Y, Birnbaumer L (2012) Jiang M (2012) Go2Gprotein mediates galanin inhibitory effects on insulin release from pancreatic 훽 cells. Proc Natl Acad Sci U S A 109:2636–2641CrossRefPubMedPubMedCentral
go back to reference Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, Castaneda TR, Muzzin P, Schurmann A, Szanto I, Tschop MH, Rohner-Jeanrenaud F (2006) Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 116:1983–1993CrossRefPubMedPubMedCentral Theander-Carrillo C, Wiedmer P, Cettour-Rose P, Nogueiras R, Perez-Tilve D, Pfluger P, Castaneda TR, Muzzin P, Schurmann A, Szanto I, Tschop MH, Rohner-Jeanrenaud F (2006) Ghrelin action in the brain controls adipocyte metabolism. J Clin Invest 116:1983–1993CrossRefPubMedPubMedCentral
go back to reference Wittmann G, Sarkar S, Hrabovszky E, Liposits Z, Lechan RM, Fekete C (2004) Galanin- but not galanin-like peptide-containing axon terminals innervate hypophysiotropic TRH-synthesizing neurons in the hypothalamic paraventricular nucleus. Brain Res 1002:43–50CrossRefPubMed Wittmann G, Sarkar S, Hrabovszky E, Liposits Z, Lechan RM, Fekete C (2004) Galanin- but not galanin-like peptide-containing axon terminals innervate hypophysiotropic TRH-synthesizing neurons in the hypothalamic paraventricular nucleus. Brain Res 1002:43–50CrossRefPubMed
go back to reference Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992–5995CrossRefPubMed Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992–5995CrossRefPubMed
go back to reference Yang Y, Atasoy D, Su HH, Sternson SM (2011) Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell 146:992–1003CrossRefPubMedPubMedCentral Yang Y, Atasoy D, Su HH, Sternson SM (2011) Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell 146:992–1003CrossRefPubMedPubMedCentral
Metadata
Title
The central effect of 3-iodothyronamine on brain neuropeptides in mice
Authors
N. Kazemipour
N. Eskandarzade
R. Beigi
S. Nazifi
Publication date
01-09-2017
Publisher
Springer London
Published in
Comparative Clinical Pathology / Issue 5/2017
Print ISSN: 1618-5641
Electronic ISSN: 1618-565X
DOI
https://doi.org/10.1007/s00580-017-2495-2

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