To further functional study we found

To further functional study, we found that the mRNA levels of fatty AH 7614 receptor β-oxidation–related genes such as ACSL1, CPT1, CACT, and HADHB were increased after PA treatment and regulated by PKCζ (Figure 5). The SIRT6 RNAi and T294A mutant SIRT6 transfected study also showed that phosphorylation SIRT6 at Thr294 residue is a key point on the regulation of PA-induced gene expression of fatty acid β-oxidation–related genes (Figure 6A, B). In further study of the mechanism, we found that the binding of SIRT6 to the ACSL1, CPT1, CACT, and HADHB promoters was increased after PA treatment and regulated by PKCζ through SIRT6 phosphorylation (Figure 6C-J). Recently, Khan et al. showed that SIRT6 transcriptionally regulated the expression of pyruvate dehydrogenase kinase 4 by binding to its promoter to further mediate glucose metabolism in heart [49]. SIRT6 transcriptional activation is less reported, but one study has shown that SIRT6 can interact with and recruit RNAP II to coactivate nuclear factor erythroid 2-related factor 2 in human mesenchymal stem cells [50]. It needs to be further explored whether SIRT6 can recruit certain activator to the promoters of fatty acid β-oxidation–related genes to regulate fatty acid β-oxidation. Taken together, we have identified a novel function of PKCζ on fatty acid β-oxidation. We found that PKCζ physically interacts with SIRT6 in vitro and in vivo, and phosphorylates SIRT6 at Thr294 residue after PA treatment. PKCζ mediated SIRT6 phosphorylation could recruit SIRT6 to the promoters of fatty acid β-oxidation–related genes and further regulated the expression of these genes. Understanding the new role of PKCζ on fatty acid β-oxidation will be useful for the future design of effective therapeutic targets to help regulate lipid homeostasis or treat metabolic diseases.
Financial Support We would like to acknowledge financial support by the National Natural Science Foundation of China (grant numbers 81672778 and 81372165) and Natural Science Foundation of Beijing Municipality (grant number 5142009).
Acknowledgements
Introduction The process of spermatogenesis and consequently male fertility is dependent upon the somatic cells that are present in the testis. Leydig cells are essential because of androgen production, and Sertoli cells are absolutely necessary in order to provide an adequate and protected environment within the seminiferous tubules. Sertoli cell carbohydrate metabolism presents some interesting characteristics. Glucose is metabolized to lactate since germ cells situated beyond the blood testis barrier rely on Sertoli cell production of this hydroxyacid to obtain energy (Boussouar and Benahmed, 2004). Hence, glucose is not an essential source of energy for Sertoli cells; in fact it has been shown that this cell type can survive in culture for at least 48h in the absence of glucose (Riera et al., 2009). In this metabolic context, it has been shown that the oxidation of fatty acids (FA) can yield much of the energy required by Sertoli cells (Jutte et al., 1985).