scholarly journals Hepatic Gene Expression Profiling in Nrf2 Knockout Mice after Long-Term High-Fat Diet-Induced Obesity

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Dionysios V. Chartoumpekis ◽  
Panos G. Ziros ◽  
Apostolos Zaravinos ◽  
Ralitsa P. Iskrenova ◽  
Agathoklis I. Psyrogiannis ◽  
...  

Introduction. The transcription factor NFE2-related factor 2 (Nrf2) is a central regulator of antioxidant and detoxification gene expression in response to electrophilic or oxidative stress. Nrf2 has recently been shown to cross-talk with metabolic pathways, and its gene deletion protected mice from high-fat-diet-(HFD-) induced obesity and insulin resistance. This study aimed to identify potential Nrf2-regulated genes of metabolic interest by comparing gene expression profiles of livers of wild-type (WT) versus Nrf2 knockout (Nrf2-KO) mice after a long-term HFD.Methods. WT and Nrf2-KO mice were fed an HFD for 180 days; total RNA was prepared from liver and used for microarray analysis and quantitative real-time RT-PCR (qRT-PCR).Results. The microarray analysis identified 601 genes that were differentially expressed between WT and Nrf2-KO mice after long-term HFD. Selected genes, including ones known to be involved in metabolic regulation, were prioritized for verification by qRT-PCR:Cyp7a1andFabp5were significantly overexpressed in Nrf2-KO mice; in contrast,Car,Cyp2b10,Lipocalin 13,Aquaporin 8,Cbr3,Me1, andNqo1were significantly underexpressed in Nrf2-KO mice.Conclusion. Transcriptome profiling after HFD-induced obesity confirms thatNrf2is implicated in liver metabolic gene networks. The specific genes identified here may provide insights into Nrf2-dependent mechanisms of metabolic regulation.

Gene ◽  
2004 ◽  
Vol 340 (1) ◽  
pp. 99-109 ◽  
Author(s):  
Sujong Kim ◽  
Insuk Sohn ◽  
Joon-Ik Ahn ◽  
Ki-Hwan Lee ◽  
Yeon Sook Lee ◽  
...  

2018 ◽  
Vol 19 (10) ◽  
pp. 2855 ◽  
Author(s):  
Jewon Jung ◽  
Dong-In Kim ◽  
Gi-Youn Han ◽  
Hyung Kwon

High-fat diet (HFD) often causes obesity and it has detrimental effects on the sensory system. In particular, sensory-mediated responses are crucial for maintaining energy balance, as they are involved in a metabolic regulation; however, there is still no clear explanation about the relationship between HFD-induced stress and sensory system. To gain insight on how HFD-induced stress affects olfactory sensitivity and behavioral responses, we have used a Drosophila melanogaster model for olfactory and nutrient-related signaling and accessed physiological, behavioral, and transcriptional changes. We demonstrated that lifespan and climbing ability in HFD-treated flies decreased and that olfactory sensitivity and behavioral responses to odorants were changed. Olfactory sensitivity to eight of ten odorants after 14 days on HFD treatment were reduced, while behavioral attraction was increased to benzaldehyde in flies that were treated with HFD. This behavioral and physiological modification in HFD-treated flies for 14 days was accompanied by a significant decrease in DmOrco gene expression in a peripheral olfactory organ, suggesting that is could be involved in the action of metabolic and sensory signal. Gene expression profiles of antennae showed significant differences on the olfactory receptors, odorant-binding proteins, and insulin signaling. Our results suggested that olfactory sensitivity and behavioral responses to HFD-induced stress are mediated through olfactory and nutrient-related signaling pathways.


2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Yun Jung Bae ◽  
Youn-Kyung Bak ◽  
Taesun Park ◽  
Myung-Sook Choi ◽  
Jeongseon Kim ◽  
...  

2016 ◽  
Vol 310 (11) ◽  
pp. E886-E899 ◽  
Author(s):  
Pia Kiilerich ◽  
Lene Secher Myrmel ◽  
Even Fjære ◽  
Qin Hao ◽  
Floor Hugenholtz ◽  
...  

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Dragan Milenkovic ◽  
Agnieszka Gomułkiewicz ◽  
Cecile Gladine ◽  
Dariusz Janczak ◽  
Irmina Grzegorek ◽  
...  

Abstract Objectives We have previously shown that 12 months (mo.) high-fat diet (HFD) in pigs led to pathophysiological alterations, incl. fattening and increased femoral artery intima-media-thickness, which were partly reversed after 3 mo. return to control diet (Zabek et al., PLoS One 2017). The aim of this study was to decipher underlying mechanism of action of these dietary interventions on the arteries by nutrigenomics analyses of intima and media of aorta. Methods 32 female pigs were divided into 3 groups: Control diet (CD) for 12 mo; HFD for 12 mo; 3) Reversal diet group (RD): HFD for 9 mo followed by CD for 3 mo After 12 mo animals were killed and abdominal aorta collected. RNA was isolated from aorta intima and media for whole genome microarray analyses followed by bioinformatics analyses. Results HFD compared to CD group significantly affected gene expression profile in intima with genes belonging to the chemotaxis, inflammation or endothelial permeability. RD induced gene expression profile was distinct from the CD group. This suggests that 3 mo of reversal to CD is not sufficient to correct gene expression changes induced by HFD. Comparison of RD profile with that of HFD group revealed a group of genes with opposite expression, e.g., genes regulating inflammation, toll-like cell signaling pathway or cytoskeleton organization involved in the regulation of cell permeability. This suggests that return to the RD only partly restored gene expression alterations due to the HFD. Significant changes in expression of genes in media following HFD were also observed, such as genes involved in cytoskeleton organization and migration MAPK signaling. As for intima, the expression profile of media of pigs on RD was different on that of these on CD diet. Compared to HFD, a group of genes involved in PI3K or MAPK pathways presented opposite expression suggesting that RD can partly correct the changes in genomic effect induced by HFD. Conclusions This study revealed genomic modifications induced by long-term HFD consumption on arterial intima and media. The return to normal diet for 3 mo was not sufficient to counteract the genomic effect of long-term HFD consumption. Funding Sources WROVASC Integrated Cardiovascular Centre, co-financed by the European Regional Development Fund.


Gene ◽  
2015 ◽  
Vol 565 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Hyeng-Soo Kim ◽  
Zae Young Ryoo ◽  
Sang Un Choi ◽  
Sanggyu Lee

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhe Wang ◽  
Ming Zhu ◽  
Meng Wang ◽  
Yihui Gao ◽  
Cong Zhang ◽  
...  

BackgroundThe number of diet induced obese population is increasing every year, and the incidence of type 2 diabetes is also on the rise. Histone methylation and acetylation have been shown to be associated with lipogenesis and obesity by manipulating gene expression via the formation of repression or activation domains on chromosomes.ObjectiveIn this study, we aimed to explore gene activation or repression and related biological processes by histone modification across the whole genome on a high-fat diet (HFD) condition. We also aimed to elucidate the correlation of these genes that modulated by histone modification with energy metabolism and inflammation under both short-term and long-term HFD conditions.MethodWe performed ChIP-seq analysis of H3K9me2 and H3K9me3 in brown and white adipose tissues (WATs; subcutaneous adipose tissue) from mice fed with a standard chow diet (SCD) or HFD and a composite analysis of the histone modification of H3K9me2, H3K9me3, H3K4me1 and H3K27ac throughout the whole genome. We also employed and integrated two bulk RNA-seq and a single-nuclei RNA sequencing dataset and performed western blotting (WB) to confirm the gene expression levels in adipose tissue of the SCD and HFD groups.ResultsThe ChIP-seq and transcriptome analysis of mouse adipose tissues demonstrated that a series of genes were activated by the histone modification of H3K9me2, H3K9me3, H3K4me1, and H3K27ac in response to HFD condition. These genes were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in lipogenesis, energy metabolism and inflammation. Several genes in the activated mitogen-activated protein kinase (MAPK) pathway might be related to both inflammation and energy metabolism in mice, rats and humans fed with HFD for a short or long term, as showed by bulk RNA-seq and single nuclei RNA-seq datasets. Western blot analyses further confirmed the increased expression of MET, VEGFA and the enhanced phosphorylation ratio of p44/42 MAPK upon HFD treatment.ConclusionThis study expanded our understanding of the influence of eating behavior on obesity and could assist the identification of putative therapeutic targets for the prevention and treatment of metabolic disorders in the future.


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