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Feeding and glucagon‐like peptide ‐1 receptor activation stabilise β‐catenin in specific hypothalamic nuclei in male rats
Author(s) -
McEwen H. J. L.,
Cognard E.,
Ladyman S. R.,
KhantAung Z.,
Tups A.,
Shepherd P. R.,
Grattan D. R.
Publication year - 2018
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12607
Subject(s) - medicine , endocrinology , catenin , hypothalamus , biology , wnt signaling pathway , beta catenin , signal transduction , phosphorylation , adherens junction , glucose homeostasis , microbiology and biotechnology , insulin , cadherin , cell , insulin resistance , biochemistry
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.