Send to

Choose Destination
J Neuroendocrinol. 2018 May 11:e12607. doi: 10.1111/jne.12607. [Epub ahead of print]

Feeding and GLP-1 receptor activation stabilize β-catenin in specific hypothalamic nuclei in male rats.

Author information

Centre for Neuroendocrinology, University of Otago, Dunedin, New Zealand.
Department of Anatomy, University of Otago, Dunedin, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, New Zealand.
Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
Department of Physiology, University of Otago, Dunedin, New Zealand.


β-catenin is a multifunctional protein that can act in the canonical Wnt/β-catenin pathway to regulate gene expression but can also bind to cadherin proteins in adherens junctions where it plays a key role in regulating cytoskeleton linked with these junctions. Recently, evidence has been presented indicating an essential role for β-catenin in regulating trafficking of insulin vesicles in β-cells and showing that changes in nutrient levels rapidly alter levels of β-catenin in these cells. Given the importance of neuroendocrine hormone secretion in the regulation of whole body glucose homeostasis, the objective of this study was to investigate whether β-catenin signalling is regulated in the hypothalamus during the normal physiological response to food intake. Rats were subjected to a fasting/re-feeding paradigm, and then samples collected at specific timepoints for analysis of β-catenin expression by immunohistochemistry and Western blotting. Changes in gene expression were assessed by RT-qPCR. Using immunohistochemistry, feeding acutely increased detectable cytoplasmic levels of β-catenin ('stabilized β-catenin') in neurons in specific regions of the hypothalamus involved in metabolic regulation, including the arcuate, dorsomedial and paraventricular nuclei of the hypothalamus. Feeding-induced elevations in β-catenin in these nuclei were associated with increased transcription of several genes that are known to be responsive to Wnt/β-catenin signalling. The effect of feeding was mimicked by administration of the GLP-1 agonist exendin-4, and was characterized by cAMP-dependent phosphorylation of β-catenin at serine residues 552 and 675. The data suggest that β-catenin/TCF signalling is involved in metabolic sensing in the hypothalamus. This article is protected by copyright. All rights reserved.


Wnt/beta catenin; arcuate nucleus; glucose homeostasis; hypothalamus


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center