Growth Differentiation Factor 11 exacerbates non-alcoholic fatty liver disease in vitro and in vivo
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ABSTRACT:
PROVIDER: PRJNA560078 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9962060.fastq.gz | Fastqsanger.gz | |||
| SRR9962055.fastq.gz | Fastqsanger.gz | |||
| SRR9962056.fastq.gz | Fastqsanger.gz | |||
| SRR9962057.fastq.gz | Fastqsanger.gz | |||
| SRR9962058.fastq.gz | Fastqsanger.gz |
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Project description:Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11) is a member of the Growth differentiation factors (GDFs), a subfamily of proteins belonging to the transforming growth factor-beta (TGF-β) superfamily (Katoh and Katoh 2006). ). In the past 7-8 years, several high profile studies, showed that systemic restoration of GDF11 levels reverses age-related phenotypes and rejuvenated heart and skeletal muscle in aged mice (Loffredo, Steinhauser et al. 2013, Sinha, Jang et al. 2014), improves insulin sensitivity via restoring pancreatic β-cell function in diabetic mice (Li, Li et al. 2017), and increases proliferation of brain capillary endothelial cells thereby improving the vascular and neurogenic rejuvenation in the brain of aged mice (Katsimpardi, Litterman et al. 2014, Finkenzeller, Stark et al. 2015, Zhang, Guo et al. 2018). Nonetheless, the possible rejuvenation effect of GDF11 was questioned over past years by several other studies. These reports doubted the age-associated decrease of circulating GDF11 level and related phenotypes in the muscle, the heart and the brain (Egerman, Cadena et al. 2015, Rodgers and Eldridge 2015); moreover, restoration of GDF11 levels in old mice had no positive effect on heart structure or function (Smith, Zhang et al. 2015). Increase of GDF11 levels had deleterious effects on aging skeletal muscle regeneration (Egerman, Cadena et al. 2015), suggesting also that supraphysiological levels could lead to cachexia (Hammers, Merscham-Banda et al. 2017). In the field of liver diseases, GDF11 was shown to exhibit tumor suppressive properties in HCC cells (Zhang, Pan et al. 2018, Gerardo-Ramírez, Lazzarini-Lechuga et al. 2019) and to worsen hepatocellular injury and liver regeneration after liver ischemia reperfusion injury (Liu, Dong et al. 2018). From these controverted studies, it is clear that the systemic effects of GDF11 in health and disease are not yet clearly and fully delineated. The aim of the present study was to specifically characterize the role of GDF11 in lipid metabolism and in the progression of the NAFLD disease spectrum, which is currently unknown. We thus aimed at investigating the potential effect of GDF11 on lipid droplet formation in human hepatocytes. Our data strongly suggest that GDF11 supplementation exacerbates, both in presence or absence of FFA, lipid droplet accumulation in two hepatic cell models (HepG2 and Hep3B) by impinging on ALK5/SMAD2/3 dependent signaling pathway.
2019-08-14 | GSE135796 | GEO
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes. There are 12 samples in our study which belonged to 4 groups, and each group contains 3 different samples.
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Project description:Human hepatocyte PNPLA3 148M exacerbates rapid non-alcoholic fatty liver disease development in chimeric mice
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Project description:Purpose: The goals of this study were to identify preferential gene expression signatures that are unique to hepatic macrophages in high-fat diet -induced non-alcoholic fatty liver disease. Methods and results: Wild-type and Casp11-/- mice were treated with high fat and normal chow diet for a period of 12 weeks. Hepatic macrophages from liver were isolated to generate mRNA transcription. Conclusion: Our study represents detailed analysis of caspase-11 in regulating hepatic macrophages in high-fat diet -induced non-alcoholic fatty liver disease.
2023-01-17 | GSE221005 | GEO
Project description:Non-alcoholic fatty liver (NAFL) has the potential to progress to non-alcoholic steatohepatitis (NASH) or to promote type 2 diabetes mellitus (T2DM). However, NASH and T2DM do not always develop coordinately. We established rat models of NAFL, NASH, and NAFL + T2DM to recapitulate different phenotypes associated with NAFLD and its progression. Microarrays were used to identify hepatic gene expression changes in each of these models. The goal is to identify a predictor of different NAFLD progressions. Non-alcoholic fatty liver disease (NAFLD) is recognized as a low-grade systemic inflammatory state with both hepatic and extra-hepatic manifestations. We aimed to identify common key regulators and adaptive pathways in different NAFLD phenotypes. NAFL, NASH and NAFL+T2DM rat models were used to represent simple fatty liver, fatty liver with severe hepatic manifestations, and fatty liver with severe metabolic manifestations, respectively. We applied microarray analysis to characterize the key regulators and adaptive pathways in different NAFLD phenotypes.
2015-01-23 | GSE65220 | GEO
Project description:To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR), we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages. Five-week-old C3H/HeN female mice (CLEA, Japan) were acclimated to the maintenance condition (25°C, 8:00-20:00 day / 20:00-8:00 night cycle and 35~40 % humidity), fed a CE-2 diet (CLEA, Japan), and given water ad libitum for one week. Each group of mice (n=4 for wild type mice analysis and n=3 for CAR decficient mice analysis) was fed Lieber's isocaloric diet (Oriental yeast, Japan) containing water, containing ethanol, containing ethanol and ellagic acid (Fluka Biochemika, Switzerland), or containing ethanol and trans-resveratrol (Sigma, USA) (Supplementary Table 1) for one week at 10:00 ad libitum. Then, the mice were fed each diet at 12 g / day for four weeks (Supplementary Fig. 1A). The approximate intake of each polyphenol was 50 mg / kg body weight / day. At 10:00 of the final day of the experimental period, the animals were anesthetized by diethyl ether, sacrificed by cervial fracture, and the heart blood, and the liver were collected.
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Project description:Global gene expression patterns of 2 human steatosis and 9 human non-alcoholic steatohepatitis (NASH) together with their respective control patterns were analyzed to define the non-alcoholic fatty liver disease (NAFLD) progression molecular characteristics and to define NASH early markers from steatosis.
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Project description:Simple steatosis (SS) and non-alcoholic steatohepatitis (NASH) are subtypes of non-alcoholic fatty liver disease. The difference in pathogenesis between SS and NASH is still not clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that regulate gene expression. The aim of this study was to examine the relationship of miRNA expression profiles with SS and NASH in animal models and humans.
2016-01-01 | GSE69670 | GEO
Project description:To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR), we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages.
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