Abstract
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.
Highlights
Aging is a complex process characterized by a general and irreversible decline in an organism’s fitness and capacity to survive
Hepatic JAZF zinc finger 1 (JAZF1) is down-regulated in human nonalcoholic fatty liver disease (NAFLD) and obesity-related mice To investigate whether JAZF1 is involved in hepatic steatosis, we examined hepatic JAZF1 expression in db/ db mice, C57BL/6 J fed with high fat diet (HFD) and adiponectin knockout (Adipoq KO) mice, and patients with NAFLD
Abdominal fat, fasting blood glucose (FBG), cholesterol, triglyceride, free fatty acid (FFA), alanine transaminase (ALT) and aspartate transaminase (AST) were markedly elevated in 2 + 6 and/ or 2 + 12 month-old C57BL/6 J and JAZF1 mice when fed standard diet (SD) compare to 2 + 3 month-old littermates (P < 0.05 or P < 0.01)
Summary
Aging is a complex process characterized by a general and irreversible decline in an organism’s fitness and capacity to survive. Western blot analyses showed that the protein levels of hepatic SREBP-1 and FAS were significantly decreased in JAZF1-Tg mice compared with age-matched WT mice (Fig. 1d).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
