TY - JOUR
T1 - JAZF1 ameliorates age and diet-associated hepatic steatosis through SREBP-1c -dependent mechanism
AU - Wei, Qin
AU - Zhou, Baoyong
AU - Yang, Gangyi
AU - Hu, Wenjing
AU - Zhang, Lili
AU - Liu, Rui
AU - Li, Minyan
AU - Wang, Kuan
AU - Gu, Harvest F.
AU - Guan, Youfei
AU - Zhu, Zhiming
AU - Zheng, Hongting
AU - Peng, Jun
AU - Li, Ling
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/9/1
Y1 - 2018/9/1
N2 - JAZF zinc finger 1 (JAZF1) is involved in glucose and lipid metabolisms. However, its role in aging- and nutrient-related hepatic steatosis is unclear. In the current study, we demonstrated that JAZF1 expression was markedly down-regulated in obesity-associated mice and nonalcoholic fatty liver disease (NAFLD) patients. During aging, JAZF1 expression was gradually down-regulated in both C57BL/6 J and JAZF1-Tg mice. In JAZF1-Tg mice, body fat content and hepatosteatosis were protected from HFD-induced steatosis, and accompanied by decreased lipogenesis gene expression. The inhibitory effects of hepatic steatosis in JAZF1-Tg mice, however, were disappeared during aging. In hepatocytes, over-expression of JAZF1 attenuated, while knockdown of JAZF1 enhanced the expression of lipogenesis genes. The over-expressing of JAZF1 in hepatocytes displayed the increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased sterol regulatory element-binding protein 1c (SREBP-1c) expression. The roles of JAZF1 were partially attenuated by Compound C. Mechanistically, JAZF1 suppressed SREBP-1c expression through the inhibition of transcriptional activity of liver X receptor response elements (LXREs) in the SREBP-1c promoter. Data illustrate that JAZF1 may have a crucial role in the regulation of age and nutrient-associated hepatosteatosis through an AMPK/SREBP-1c-dependent mechanism.
AB - JAZF zinc finger 1 (JAZF1) is involved in glucose and lipid metabolisms. However, its role in aging- and nutrient-related hepatic steatosis is unclear. In the current study, we demonstrated that JAZF1 expression was markedly down-regulated in obesity-associated mice and nonalcoholic fatty liver disease (NAFLD) patients. During aging, JAZF1 expression was gradually down-regulated in both C57BL/6 J and JAZF1-Tg mice. In JAZF1-Tg mice, body fat content and hepatosteatosis were protected from HFD-induced steatosis, and accompanied by decreased lipogenesis gene expression. The inhibitory effects of hepatic steatosis in JAZF1-Tg mice, however, were disappeared during aging. In hepatocytes, over-expression of JAZF1 attenuated, while knockdown of JAZF1 enhanced the expression of lipogenesis genes. The over-expressing of JAZF1 in hepatocytes displayed the increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and decreased sterol regulatory element-binding protein 1c (SREBP-1c) expression. The roles of JAZF1 were partially attenuated by Compound C. Mechanistically, JAZF1 suppressed SREBP-1c expression through the inhibition of transcriptional activity of liver X receptor response elements (LXREs) in the SREBP-1c promoter. Data illustrate that JAZF1 may have a crucial role in the regulation of age and nutrient-associated hepatosteatosis through an AMPK/SREBP-1c-dependent mechanism.
UR - https://www.scopus.com/pages/publications/85052398219
U2 - 10.1038/s41419-018-0923-0
DO - 10.1038/s41419-018-0923-0
M3 - 文章
C2 - 30154417
AN - SCOPUS:85052398219
SN - 2041-4889
VL - 9
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 9
M1 - 859
ER -
