» Articles » PMID: 23645151

Amylin Acts in the Central Nervous System to Increase Sympathetic Nerve Activity

Overview
Journal Endocrinology
Specialty Endocrinology
Date 2013 May 7
PMID 23645151
Citations 16
Authors
Affiliations
Soon will be listed here.
Abstract

The pancreatic hormone amylin acts in the central nervous system (CNS) to decrease food intake and body weight. We hypothesized that amylin action in the CNS promotes energy expenditure by increasing the activity of the sympathetic nervous system. In mice, ip administration of amylin significantly increased c-Fos immunoreactivity in hypothalamic and brainstem nuclei. In addition, mice treated with intracerebroventricular (icv) amylin (0.1 and 0.2 nmol) exhibited a dose-related decrease in food intake and body weight, measured 4 and 24 hours after treatment. The icv injection of amylin also increased body temperature in mice. Using direct multifiber sympathetic nerve recording, we found that icv amylin elicited a significant and dose-dependent increase in sympathetic nerve activity (SNA) subserving thermogenic brown adipose tissue (BAT). Of note, icv injection of amylin also evoked a significant and dose-related increase in lumbar and renal SNA. Importantly, icv pretreatment with the amylin receptor antagonist AC187 (20 nmol) abolished the BAT SNA response induced by icv amylin, indicating that the sympathetic effects of amylin are receptor-mediated. Conversely, icv amylin-induced BAT SNA response was enhanced in mice overexpressing the amylin receptor subunit, RAMP1 (receptor-activity modifying protein 1), in the CNS. Our data demonstrate that CNS action of amylin regulates sympathetic nerve outflow to peripheral tissues involved in energy balance and cardiovascular function.

Citing Articles

Mediators of Amylin Action in Metabolic Control.

Boyle C, Zheng Y, Lutz T J Clin Med. 2022; 11(8).

PMID: 35456307 PMC: 9025724. DOI: 10.3390/jcm11082207.


Mouse Microglial Calcitonin Receptor Knockout Impairs Hypothalamic Amylin Neuronal pSTAT3 Signaling but Lacks Major Metabolic Consequences.

Coester B, Lutz T, Le Foll C Metabolites. 2022; 12(1).

PMID: 35050175 PMC: 8780059. DOI: 10.3390/metabo12010051.


The long-acting amylin/calcitonin receptor agonist ZP5461 suppresses food intake and body weight in male rats.

Stein L, McGrath L, Lhamo R, Koch-Laskowski K, Fortin S, Skarbaliene J Am J Physiol Regul Integr Comp Physiol. 2021; 321(2):R250-R259.

PMID: 34259025 PMC: 8409915. DOI: 10.1152/ajpregu.00337.2020.


Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?.

Genchi V, DOria R, Palma G, Caccioppoli C, Cignarelli A, Natalicchio A Int J Mol Sci. 2021; 22(12).

PMID: 34208585 PMC: 8235268. DOI: 10.3390/ijms22126445.


An inducible model of human amylin overexpression reveals diverse transcriptional changes.

Aldras Y, Singh S, Bode K, Bhowmick D, Jeremic A, OHalloran D Neurosci Lett. 2019; 704:212-219.

PMID: 30974231 PMC: 6594890. DOI: 10.1016/j.neulet.2019.04.016.


References
1.
Kailasam M, Parmer R, Tyrell E, Henry R, OConnor D . Circulating amylin in human essential hypertension: heritability and early increase in individuals at genetic risk. J Hypertens. 2000; 18(11):1611-20. DOI: 10.1097/00004872-200018110-00012. View

2.
Paxinos G, Chai S, Christopoulos G, Huang X, Toga A, Wang H . In vitro autoradiographic localization of calcitonin and amylin binding sites in monkey brain. J Chem Neuroanat. 2004; 27(4):217-36. DOI: 10.1016/j.jchemneu.2004.03.005. View

3.
Hay D, Christopoulos G, Christopoulos A, Sexton P . Amylin receptors: molecular composition and pharmacology. Biochem Soc Trans. 2004; 32(Pt 5):865-7. DOI: 10.1042/BST0320865. View

4.
Osaka T, Tsukamoto A, Koyama Y, Inoue S . Central and peripheral administration of amylin induces energy expenditure in anesthetized rats. Peptides. 2008; 29(6):1028-35. DOI: 10.1016/j.peptides.2008.02.002. View

5.
Rushing P, Hagan M, Seeley R, Lutz T, Woods S . Amylin: a novel action in the brain to reduce body weight. Endocrinology. 2000; 141(2):850-3. DOI: 10.1210/endo.141.2.7378. View