Adiponectin inhibits Wnt co-receptor, Lrp6, phosphorylation and beta-catenin signaling

作者：Reinke Lauren; Lam Anna P; Flozak Annette S; Varga John; Gottardi Cara J^*

来源：Biochemical and Biophysical Research Communications, 2016, 470(3): 606-612.

DOI：10.1016/j.bbrc.2016.01.097

• Fibrosis
• Metabolism
• Obesity
• Metabolic syndrome
• Cardiovascular disease
• Adiponectin
• Wnt
• Beta catenin signaling
• Lrp5/6 receptors

Adiponectin is a pleiotropic adipokine implicated in obesity, metabolic syndrome and cardiovascular disease. Recent studies have identified adiponectin as a negative regulator of tissue fibrosis. Wnt/beta-catenin signaling has also been implicated in metabolic syndrome and can promote tissue fibrosis, but the extent to which adiponectin cross-regulates Wnt/beta-catenin signaling is unknown. Using primary human dermal fibroblasts and recombinant purified proteins, we show that adiponectin can limit beta-catenin accumulation and downstream gene activation by inhibiting Lrp6 phosphorylation, a key activation step in canonical Wnt signaling. Inhibition of Wnt3a-mediated Lrp6 phospho-activation is relatively rapid (e.g., by 30 min), and is not dependent on established adiponectin G-protein coupled receptors, AdipoR1 and R2, suggesting a more direct relationship to Lrp6 signaling. In contrast, the ability of adiponectin to limit Wnt-induced and baseline collagen production in fibroblasts requires AdipoR1/R2. These results suggest the possibility that the pleiotropic effects of adiponectin may be mediated through distinct cell surface receptor complexes. Accordingly, we propose that the anti-fibrotic activity of adiponectin may be mediated through AdipoR1/R2 receptors, while the ability of adiponectin to inhibit Lrp6 phospho-activation may be relevant to other recently established roles for Lrp6 signaling in glucose metabolism and metabolic syndrome. Published by Elsevier Inc.

• 出版日期2016-2-12
• 单位西北大学