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

Biochemical and Biophysical Research Communications
Lauren ReinkeCara J Gottardi

Abstract

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/β-catenin signaling has also been implicated in metabolic syndrome and can promote tissue fibrosis, but the extent to which adiponectin cross-regulates Wnt/β-catenin signaling is unknown. Using primary human dermal fibroblasts and recombinant purified proteins, we show that adiponectin can limit β-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 thr...Continue Reading

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Citations

Nov 26, 2016·Matrix Biology : Journal of the International Society for Matrix Biology·Susann JunkerElena Neumann
Jul 2, 2017·Scientific Reports·Roberta G MarangoniJohn Varga
Oct 22, 2019·Biophysical Journal·Michael L SalinasRobert S Chapkin
Oct 6, 2020·Aging and Disease·Ni ZengGuo-Xin Ni
Oct 6, 2021·Journal of Cellular Physiology·Si-Yu LiuXia Li

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