Feeding and glucagon-like peptide-1 receptor activation stabilise β-catenin in specific hypothalamic nuclei in male rats
Date
2018
Authors
McEwen, H.J.L.
Cognard, E.
Ladyman, S.R.
Khant Aung, Z.
Tups, A.
Shepherd, P.R.
Grattan, D.R.
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Journal article
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Journal of Neuroendocrinology, 2018; 30(6):1-10
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Abstract
β-catenin is a multifunctional protein that not only acts in the canonical Wnt/β-catenin pathway to regulate gene expression but also binds 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 the 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 present study aimed 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 were collected at specific timepoints for analysis of β-catenin expression by immunohistochemistry and western blotting. Changes in gene expression were assessed by a quantitative reverse transcriptase-polymerase chain reaction. Using immunohistochemistry, feeding acutely increased detectable cytoplasmic levels of β-catenin (‘stabilised β-catenin’) in neurones 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 an increased transcription of several genes 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 also characterised by cAMP-dependent phosphorylation of β-catenin at serine residues 552 and 675. These data suggest that β-catenin/T cell factor signalling is involved in metabolic sensing in the hypothalamus.
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Copyright 2018 British Society for Neuroendocrinology