%0 Journal Article %T p38¦Á MAPK antagonizing JNK to control the hepatic fat accumulation in pediatric patients onset intestinal failure %A Jun Wang %A Kejun Zhou %A Wei Cai %A Weihui Yan %A Yi Cao %A Yongtao Xiao %J Archive of "Cell Death & Disease". %D 2017 %R 10.1038/cddis.2017.523 %X The p38¦Á mitogen-activated protein kinase (MAPK) has been related to gluconeogenesis and lipid metabolism. However, the roles and related mechanisms of p38¦Á MAPK in intestinal failure (IF)-associated liver steatosis remained poor understood. Here, our experimental evidence suggested that p38¦Á MAPK significantly suppressed the fat accumulation in livers of IF patients mainly through two mechanisms. On the one hand, p38¦Á MAPK increased hepatic bile acid (BA) synthesis by upregulating the expression of the rate-limiting enzyme cholesterol 7-¦Á-hydroxylase (CYP7A1) and peroxisome proliferator-activated receptor ¦Ã coactivator-1¦Á (PGC-1¦Á), which in turn activated the transcription of the CYP7A1. On the other hand, p38¦Á MAPK promoted fatty acid (FA) ¦Â-oxidation via upregulating peroxisome proliferator-activated receptor alpha (PPAR¦Á) and its transcriptional target genes carnitine palmitoyltransferase 1A (CPT1A) and peroxisomal acyl-coenzyme aoxidase 1 (ACOX1). Dual luciferase assays indicated that p38¦Á MAPK increased the transcription of PPAR¦Á, PGC-1¦Á and CYP7A1 by upregulating their promoters¡¯ activities. In addition, in vitro and in vivo assays indicated p38¦Á MAPK negatively regulates the hepatic steatosis by controlling JNK activation. In conculsion, our findings demonstrate that hepatic p38¦Á MAPK functions as a negative regulator of liver steatosis in maintaining BA synthesis and FAO by antagonizing the c-Jun N-terminal kinase (JNK) %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682685/