Liraglutide stimulates the β-catenin signaling cascade in mouse epididymal fat tissue

in Journal of Molecular Endocrinology
Authors:
Jianqiu Gu Department of Endocrinology and Metabolism and the Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, People’s Republic of China
Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada

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Weijuan Shao Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada

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Dinghui Liu Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada
Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China

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Jia Nuo Feng Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada

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Juan Pang Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada
Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China

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Tianru Jin Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada
Banting and Best Diabetes Centre, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada

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https://orcid.org/0000-0002-0307-7391

Correspondence should be addressed to T Jin: tianru.jin@utoronto.ca

*(J Gu and W Shao contributed equally to this work)

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Although canonical Wnt signaling pathway activation was shown to negatively regulate adipogenesis, recent investigations suggest that Wnt pathway effectors TCF7L2 and β-catenin (β-cat) in adipose tissues are also involved in energy homeostasis during adulthood. In assessing the metabolic beneficial effect of GLP-1-based diabetes drugs in high-fat diet (HFD)-challenged mice, we observed that liraglutide treatment affected the expression of a battery of adipose tissue-specific genes, including those that encode adiponectin and leptin, mainly in epididymal white adipose tissue (eWAT). Fourteen-week HFD challenge repressed TCF7L2 and β-cat S675 phosphorylation in eWAT, while such repression was reversed by liraglutide treatment (150 µg/kg body weight daily) during weeks 10–14. In Glp1r−/− mice, liraglutide failed in stimulating TCF7L2 or β-cat in eWAT. We detected Glp1r expression in mouse eWAT and its level is enriched in its stromal vascular fraction (SVF). Mouse eWAT-SVF showed reduced expression of Tcf7l2 and its Tcf7l2 level could not be stimulated by liraglutide treatment; while following adipogenic differentiation, rat eWAT-SVF showed elevated Tcf7l2 expression. Direct in vitro liraglutide treatment in eWAT-SVF stimulated CREB S133, β-cat S675 phosphorylation, and cellular cAMP level. Thus, cAMP/β-cat signaling cascade can be stimulated by liraglutide in eWAT via GLP-1R expressed in eWAT-SVF.

 

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