Analysis of Sterol-Regulatory Element-Binding Protein 1c Target Genes in Mouse Liver during Aging and High-Fat Diet

Capel, Frédéric; Rolland-Valognes, Gaëlle; Dacquet, Catherine; Brun, Marion; Lonchampt, Michel; Ktorza, Alain; Lockhart, Brian P.; Galizzi, Jean‐Pierre

doi:10.1159/000350751

Cited by 19 publications

(12 citation statements)

References 69 publications

(42 reference statements)

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“…Rather, the activity of already established enhancers is differentially regulated by the diet. Pathway analysis of differentially expressed genes and DNA motif analysis of these enhancers suggested that HFD induces SREBP-, ATF-4- and C/EBP-regulated transcriptional networks, in agreement with previous reports43444546. Thus, the experimental HFD setup used in our study resulted in hyperinsulinemia and hepatosteatosis associated with specific changes in enhancer activity and gene transcription likely regulated by transcription factors such as SREBP, ATF-4 and C/EBP.…”

Section: Discussionsupporting

confidence: 91%

High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

Siersbæk

Varticovski

Yang

et al. 2017

Sci Rep

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Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers, but no significant changes in chromatin accessibility, indicating that HFD-regulated gene transcription is primarily controlled by modulating the activity of pre-established enhancers. After return to the same body weight as chow fed control mice, the fasting insulin, glucose, and hepatic triglyceride levels were fully restored to normal levels. Moreover, HFD-regulated H3K27Ac and mRNA levels returned to similar levels as control mice. These data demonstrates that the transcription regulatory landscape in the liver induced by HFD is highly dynamic and can be reversed by weight loss. This provides hope for efficient treatment of early obesity-associated changes to hepatic complications by simple weight loss intervention without persistent reprograming of the liver transcriptome.

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Section: Discussionsupporting

confidence: 91%

High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

Siersbæk

Varticovski

Yang

et al. 2017

Sci Rep

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“…Acetyl coenzyme A carboxylase (ACC) is a rate-limiting enzyme that catalyzes the first step of fatty acid synthesis and metabolism and plays an important role in the lipid metabolism. ACC1 is mainly expressed in liver and catalyzes the synthesis of long-chain fatty acids, thereby promoting the progression of hepatic steatosis [60,61,62]. In our study, POE prevented the ethanol-induced liver injury by decreasing the expression of miR-122, ACC1 mRNA and protein, and increasing the expression of LPL-mRNA and protein in rats.…”

Section: Discussionsupporting

confidence: 58%

Effects of Portulaca Oleracea Extract on Acute Alcoholic Liver Injury of Rats

Qiao

Liu

et al. 2019

Molecules

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The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.

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“…2B). SREBP1c encodes a transcription factor that binds to the sterol regulatory element-1 (SRE1), which is a decamer flanking the low-density lipoprotein receptor gene and some genes involved in sterol biosynthesis (Capel et al 2013, Kim et al 2015. CD36 contributes to fatty acids translocation (Wilson et al 2016).…”

Section: A Muciniphila Supplementation Improves Lipid Accumulation Imentioning

confidence: 99%

Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice

Zhao

Wang

et al. 2017

Journal of Molecular Endocrinology

208

174

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Abnormal shifts in the composition of gut microbiota contribute to the pathogenesis of metabolic diseases, including obesity and type 2 diabetes (T2DM). The crosstalk between gut microbes and the host affects the inflammatory status and glucose tolerance of the individuals, but the underlying mechanisms have not been elucidated completely. In this study, we treated the lean chow diet-fed mice with Akkermansia muciniphila, which is thought to be inversely correlated with inflammation status and body weight in rodents and humans, and we found that A. muciniphila supplementation by daily gavage for five weeks significantly alleviated body weight gain and reduced fat mass. Glucose tolerance and insulin sensitivity were also improved by A. muciniphila supplementation compared with the vehicle. Furthermore, A. muciniphila supplementation reduced gene expression related to fatty acid synthesis and transport in liver and muscle; meanwhile, endoplasmic reticulum (ER) stress in liver and muscle was also alleviated by A. muciniphila. More importantly, A. muciniphila supplementation reduced chronic low-grade inflammation, as reflected by decreased plasma levels of lipopolysaccharide (LPS)-binding protein (LBP) and leptin, as well as inactivated LPS/LBP downstream signaling (e.g. decreased phospho-JNK and increased IKBA expression) in liver and muscle. Moreover, metabolomics profiling in plasma also revealed an increase in anti-inflammatory factors such as α-tocopherol, β-sitosterol and a decrease of representative amino acids. In summary, our study demonstrated that A. muciniphila supplementation relieved metabolic inflammation, providing underlying mechanisms for the interaction of A. muciniphila and host health, pointing to possibilities for metabolic benefits using specific probiotics supplementation in metabolic healthy individuals.

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Analysis of Sterol-Regulatory Element-Binding Protein 1c Target Genes in Mouse Liver during Aging and High-Fat Diet

Cited by 19 publications

References 69 publications

High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

Effects of Portulaca Oleracea Extract on Acute Alcoholic Liver Injury of Rats

Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice

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