Ssu72 phosphatase is involved in immunometabolism

Abstract

Abstract Reversible protein phosphorylation is the primary type of various post-translational modifications in multiple cellular signaling pathways of eukaryotic cell. Dynamic alterations of phosphorylation state of many cellular signaling-mediated proteins including adipogenesis and thermogenesis regulate their molecular and cellular fates. Ssu72 is dual protein phosphatase that can act upon tyrosine or serine/threonine residues and transcription/RNA-processing factor. Recently, we found that Ssu72 expressed in adipose tissue, especially strongly in BAT, indicating that the potential involvement of Ssu72 in regulating BAT function. In this aspect, we generated conditional knock out mice which Ssu72 is deleted specifically in adipose tissue and found that the deficiency of Ssu72 leads to BAT dysfunction and abnormal thermoregulation compared to wild type mice. Moreover, we observed not only dramatically reduction of macrophage population but also defective M2 macrophage generation in Ssu72-deficient BAT. Notably, it has been reported that IL-4-induced M2 activation of macrophages is required for adaptive thermogenesis in mice. Thus, we further generated Ssu72-deleted macrophage mouse model. This study includes the physiological relevance of Ssu72 loss-of-function in macrophage during metabolic and thermogenic responses.