scholarly journals Multifaceted regulation of hepatic lipid metabolism by YY1

2021 ◽  
Vol 4 (7) ◽  
pp. e202000928
Author(s):  
Gang Pan ◽  
Klev Diamanti ◽  
Marco Cavalli ◽  
Ariadna Lara Gutiérrez ◽  
Jan Komorowski ◽  
...  

Recent studies suggested that dysregulated YY1 plays a pivotal role in many liver diseases. To obtain a detailed view of genes and pathways regulated by YY1 in the liver, we carried out RNA sequencing in HepG2 cells after YY1 knockdown. A rigid set of 2,081 differentially expressed genes was identified by comparing the YY1-knockdown samples (n = 8) with the control samples (n = 14). YY1 knockdown significantly decreased the expression of several key transcription factors and their coactivators in lipid metabolism. This is illustrated by YY1 regulating PPARA expression through binding to its promoter and enhancer regions. Our study further suggest that down-regulation of the key transcription factors together with YY1 knockdown significantly decreased the cooperation between YY1 and these transcription factors at various regulatory regions, which are important in regulating the expression of genes in hepatic lipid metabolism. This was supported by the finding that the expression of SCD and ELOVL6, encoding key enzymes in lipogenesis, were regulated by the cooperation between YY1 and PPARA/RXRA complex over their promoters.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A284-A284
Author(s):  
Kamrul M Hasan ◽  
Meher Parveen ◽  
Alondra Pena ◽  
Erick Galdamez Calles ◽  
Marvy Gergis ◽  
...  

Abstract Non-alcoholic fatty liver diseases (NAFLD) is the most common form of liver diseases in the USA with 30–40% of American being affected and about 12% with nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver diseases. NAFLD has been linked with insulin resistance, type2 diabetes, obesity, and cardiovascular diseases but molecular mechanisms underlying the development of NAFLD and its association with metabolic syndromes are poorly understood. In this study, we explored the role of CARF (collaborator of ARF) also known as CDKN2AIP, a novel gene of ARF-MDM2-p53 pathway in the development of NAFLD. It has been shown that, p53, beyond its tumor suppressor functions, can regulate the cellular glucose and lipid metabolism and its activation has been reported to induce hepatic steatosis in mice. However, as a regulator of p53 pathway, the role of CARF in the lipid metabolism and associated metabolic diseases has not been studied yet. Using high-fat diet (HFD) fed obesity mouse model of NAFLD we found that the expression of CARF along with Sirt1, pAMPK, and pACC was significantly decreased in the HFD induced fatty livers compared to control. Similarly, CARF expression was also down-regulated in palmitate (PA)-treated HepG2 cells, an in vitro model of steatosis. We also observed that shRNA mediated knockdown or lentiviral vector mediated overexpression of CARF induced or reduced the endogenous fat accumulation, respectively, in HepG2 cells, suggesting that CARF expression is negatively regulated in NAFLD. Additionally, we performed RNA seq analysis after CARF silencing in HepG2 cells and demonstrated that silencing of CARF altered the expression of genes regulating hepatic de novo lipogenesis, beta-oxidation, and lipid secretion all of which favor the accumulation of fat in the hepatocytes. Furthermore, genes associated with mitochondrial functions such as the TCA cycle and oxidative phosphorylation were also altered which could play a role in the development of NAFLD. Finally, we demonstrated that AAV mediated hepatic overexpression of CARF in HFD fed mouse model significantly reduced the fat accumulation in the liver as evident by H&E staining of liver sections and intrahepatic triglyceride level. Altogether we conclude that CARF plays a vital role in hepatic lipid metabolism and its downregulation perturbs lipid homeostasis leading to hepatic steatosis and the development of NAFLD.


2011 ◽  
Vol 14 (4) ◽  
pp. 516-527 ◽  
Author(s):  
Min Wan ◽  
Karla F. Leavens ◽  
Danish Saleh ◽  
Rachael M. Easton ◽  
David A. Guertin ◽  
...  

2021 ◽  
pp. 1-41
Author(s):  
Chun-Yan Fu ◽  
Yan Zhang ◽  
Wen-Bin Wang ◽  
Xiang-Fa Wei ◽  
Pei-Pei Yan ◽  
...  

Abstract This experiment was designed to investigate the effect of supplementing conjugated linoleic acid (CLA) in breeder hens diet on development and hepatic lipid metabolism of chick offspring. Hy-Line Brown breeder hens were allocated into two groups, supplemented with 0 (CT) or 0.5% CLA for 8 weeks. Offspring chicks were grouped according to the mother generation and fed for 7 days. CLA treatment had no significant influence on development, egg quality, and fertility of breeder hens, but darkened the egg yolks in shade and increased yolk sac mass compared to CT group. Addition of CLA resulted in increased body mass and liver mass, and decreased deposition of subcutaneous adipose tissue in chick offspring. The serum triglyceride (TG) and cholesterol (TC) levels of chick offspring were decreased in CLA group. CLA treatment increased the incorporation of both CLA isomers (c9t11 and t10c12) in liver of chick offspring, accompanied by the decreased hepatic TG levels, related to the significant reduction of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities and the increased of carnitine palmitoyltransferase-1 (CPT1) enzyme activity. Meanwhile, CLA treatment reduced the mRNA expression of genes related to fatty acid biosynthesis (FAS, ACC, and sterol regulatory element-binding protein-1c), and induced the expression of genes related to β-oxidative (CPT1, AMP-activated protein kinase, and peroxisome proliferator-activated receptor α) in chick offspring liver. In summary, the addition of CLA in breeder hens diet significantly increased incorporation of CLA in liver of chick offspring, which further regulate hepatic lipid metabolism.


2020 ◽  
Vol 26 (10) ◽  
pp. 1029-1041 ◽  
Author(s):  
Miao He ◽  
Cong Wang ◽  
Xiao-Hong Long ◽  
Jia-Jia Peng ◽  
Dong-Fang Liu ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e106739 ◽  
Author(s):  
Mónica B. Betancor ◽  
Elsbeth McStay ◽  
Matteo Minghetti ◽  
Hervé Migaud ◽  
Douglas R. Tocher ◽  
...  

2005 ◽  
Vol 135 (10) ◽  
pp. 2355-2361 ◽  
Author(s):  
Ann-Elise O. Jordal ◽  
Bente E. Torstensen ◽  
Stephen Tsoi ◽  
Douglas R. Tocher ◽  
Santosh P. Lall ◽  
...  

2017 ◽  
Vol 96 (8) ◽  
pp. 2965-2974 ◽  
Author(s):  
S. Li ◽  
A. Schiller Vestergren ◽  
H. Wall ◽  
S. Trattner ◽  
J. Pickova ◽  
...  

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