PPARα-Target Gene Expression Requires TIS21 /BTG2 Gene in Liver of the C57BL/6 Mice under Fasting Condition

• Published in: Molecules and cells Vol. 41; no. 2; pp. 140 - 149
• Main Authors: Hong, Allen Eugene, Ryu, Min Sook, Kim, Seung Jun, Hwang, Seung Yong, Lim, In Kyoung
• Format: Journal Article
• Language: Korean
• Published: 2018
• Subjects: starvation; BTG2; PPAR{\alpha}; liver metabolism; fatty acid oxidation
• ISSN: 1016-8478; 0219-1032

The $TIS21^{/BTG2/PC3}$ gene belongs to the antiproliferative gene (APRO) family and exhibits tumor suppressive activity. However, here we report that TIS21 controls lipid metabolism, rather than cell proliferation, under fasting condition. Using microarray analysis, whole gene expression changes were investigated in liver of TIS21 knockout (TIS21-KO) mice after 20 h fasting and compared with wild type (WT). Peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$) target gene expression was almost absent in contrast to increased lipid synthesis in the TIS21-KO mice compared to WT mice. Immunohistochemistry with hematoxylin and eosin staining revealed that lipid deposition was focal in the TIS21-KO liver as opposed to the diffuse and homogeneous pattern in the WT liver after 24 h starvation. In addition, cathepsin E expression was over 10 times higher in the TIS21-KO liver than that in the WT, as opposed to the significant reduction of thioltransferase in both adult and fetal livers. At present, we cannot account for the role of cathepsin E. However, downregulation of glutaredoxin 2 thioltransferase expression might affect hypoxic damage in the TIS21-KO liver. We suggest that the $TIS21^{/BTG2}$ gene might be essential to maintain energy metabolism and reducing power in the liver under fasting condition.