| Wnt proteins are established as important regulators of development. Among the Wnt proteins, Wnt3 a plays particularly important roles in adipogenesis and mitochondrial biogenesis. However, the mechanisms through which Wnt3 a regulates mitochondrial biogenesis and function are not well understood. In this study, Wnt3 a was confirmed to stimulate mitochondrial biogenesis by increasing the expression of mitochondrial genes and regulators as well as mitochondrial copy number in ear mesenchymal stem cell(EMSC) adipocytes. Wnt3 a mediated induction of mitochondrial biogenesis was partly through p38 MAPK/CREB signaling instead of canonical Wnt/β-catenin pathway. In addition, Wnt3 a regulates lysine acetylation of a subset of mitochondrial proteins including citrate synthase, whose activity is important for the first step of TCA cycle. As a key deacetylase in mitochondrion, decreased Sirt3 and Sirt5 protein level was observed with Wnt3 a treatment, suggesting acetylation of mitochondrial proteins including citrate synthase might be due to decreased mitochondrial deacetylase. Increased citrate synthase activity and citrate production were then discovered under same Wnt3 a treatment, indicating increase in citrate synthase activity and citrate production might result from Wnt3 a mediated acetylation of citrate synthase. Furthermore, upregulated expression of beige selective genes and UCP1 protein were detected following Wnt3 a treatment in adipocytes, revealing that Wnt3 a might also participate in driving white adipocyte into beige adipocyte. In conclusion, this study confirms Wnt3 a stimulates mitochondrial biogenesis and mitochondrial protein acetylation to further influence adipocyte metabolism. Meanwhile, our data provide first evidence that Wnt3 a alters mitochondrial protein acetylation and upregulates beige adipocyte-specific genes and UCP1 expression in EMSC adipocytes, which provide new insights into the influence of Wnt signaling on adipocyte biology. |
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