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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

1
Centre for Neuroendocrinology, University of Otago, Dunedin, New Zealand.
2
Department of Anatomy, University of Otago, Dunedin, New Zealand.
3
Maurice Wilkins Centre for Molecular Biodiscovery, New Zealand.
4
Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
5
Department of Physiology, University of Otago, Dunedin, New Zealand.

Abstract

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.

KEYWORDS:

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

PMID:
29752762
DOI:
10.1111/jne.12607

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