Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

Rodent models of leptin receptor deficiency are less sensitive to amylin

Duffy, Sonya; Lutz, Thomas A; Boyle, Christina N (2018). Rodent models of leptin receptor deficiency are less sensitive to amylin. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 315(4):R856-R865.

Abstract

The pancreatic hormone amylin is released from beta cells following nutrient ingestion and contributes to the control of body weight and glucose homeostasis. Amylin reduces food intake by activating neurons in the area postrema (AP). Amylin was also shown to synergize with the adipokine leptin, with combination therapy producing greater weight loss and food intake reduction than either hormone alone. Although amylin and leptin were initially thought to interact downstream of the AP in the hypothalamus, recent findings show that the two hormones can act on the same AP neurons, suggesting a more direct relationship. The objective of this study was to determine whether amylin action depends on functional leptin signaling. We tested the ability of amylin to induce satiation and to activate its primary target neurons in the AP in two rodent models of LepR deficiency, the db/db mouse and the Zucker diabetic fatty (ZDF) rat. When compared with wild-type (WT) mice, db/db mice exhibited reduced amylin-induced satiation, reduced amylin-induced Fos in the AP, and a lower expression of calcitonin receptor (CTR) protein, the core component of all amylin receptors. ZDF rats also showed no reduction in food intake following amylin treatment; however, unlike the db/db mice, levels of amylin-induced Fos and CTR in the AP were no different than WT rats. Our results suggest that LepR expression is required for the full anorexic effect of amylin; however, the neuronal activation in the AP seems to depend on the type of LepR mutation.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Zurich Center for Integrative Human Physiology (ZIHP)
05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Institute of Veterinary Physiology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Physiology
Health Sciences > Physiology (medical)
Uncontrolled Keywords:Fos; amylin; area postrema; leptin; meal pattern
Language:English
Date:1 October 2018
Deposited On:02 Feb 2019 14:41
Last Modified:21 Oct 2024 01:35
Publisher:American Physiological Society
ISSN:0363-6119
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/ajpregu.00179.2018
PubMed ID:30133304

Metadata Export

Statistics

Citations

Dimensions.ai Metrics
23 citations in Web of Science®
23 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 02 Feb 2019
0 downloads since 12 months
Detailed statistics

Authors, Affiliations, Collaborations

Similar Publications