Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA154749 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE30447: Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-regulated in Nonalcoholic Fatty Liver (HepG2 data) GSE30450: Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-regulated in Nonalcoholic Fatty Liver (hepatocytes data) Refer to individual Series
2011-07-07 | E-GEOD-30451 | biostudies-arrayexpress
Project description:Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-regulated in Nonalcoholic Fatty Liver
| PRJNA143279 | ENA
Project description:Foxa1 Reduces Lipid Accumulation in Human Hepatocytes and Is Down-regulated in Nonalcoholic Fatty Liver (HepG2 data)
| PRJNA154745 | ENA
Project description:Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2, however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing HMGCS2 and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolism pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance. To determine the global impact of Foxa1 on human liver gene transcription, microarray expression analyses were performed in human hepatocytes transfected with Ad-Foxa1 or Ad-Control. We used microarrays to detail the global programme of gene expression in human hepatocytes infected with Ad-Foxa1 or control adenovirus (insertless Ad-pACC).
2011-07-07 | E-GEOD-30450 | biostudies-arrayexpress
Project description:Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2, however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing HMGCS2 and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolism pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance. To determine the global impact of Foxa1 on human liver gene transcription, microarray expression analyses were performed in HepG2 cells transfected with Ad-Foxa1 or Ad-Control. We used microarrays to detail the global programme of gene expression in HepG2 cells infected with Ad-Foxa1 or control adenovirus (insertless Ad-pACC).
2011-07-07 | E-GEOD-30447 | biostudies-arrayexpress
Project description:Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2, however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing HMGCS2 and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolism pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance. To determine the global impact of Foxa1 on human liver gene transcription, microarray expression analyses were performed in human hepatocytes transfected with Ad-Foxa1 or Ad-Control.
2011-07-07 | GSE30450 | GEO
Project description:Triglyceride accumulation in nonalcoholic fatty liver (NAFL) results from unbalanced lipid metabolism which, in the liver, is controlled by several transcription factors. The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors comprises three members which play important roles in controlling both metabolism and homeostasis through the regulation of multiple target genes in the liver, pancreas and adipose tissue. In the mouse liver, Foxa2 is repressed by insulin and mediates fasting responses. Unlike Foxa2, however, the role of Foxa1 in the liver has not yet been investigated in detail. In this study, we evaluate the role of Foxa1 in two human liver cell models, primary cultured hepatocytes and HepG2 cells, by adenoviral infection. Moreover, human and rat livers were analyzed to determine Foxa1 regulation in NAFL. Results demonstrate that Foxa1 is a potent inhibitor of hepatic triglyceride synthesis, accumulation and secretion by repressing the expression of multiple target genes of these pathways (e.g., GPAM, DGAT2, MTP, APOB). Moreover, Foxa1 represses the fatty acid transporter FATP2 and lowers fatty acid uptake. Foxa1 also increases the breakdown of fatty acids by inducing HMGCS2 and ketone body synthesis. Finally, Foxa1 is able to largely up-regulate UCP1, thereby dissipating energy and consistently decreasing the mitochondria membrane potential. We also report that human and rat NAFL have a reduced Foxa1 expression, possibly through a protein kinase C-dependent pathway. We conclude that Foxa1 is an antisteatotic factor that coordinately tunes several lipid metabolism pathways to block triglyceride accumulation in hepatocytes. However, Foxa1 is down-regulated in human and rat NAFL and, therefore, increasing Foxa1 levels could protect from steatosis. Altogether, we suggest that Foxa1 could be a novel therapeutic target for NAFL disease and insulin resistance. To determine the global impact of Foxa1 on human liver gene transcription, microarray expression analyses were performed in HepG2 cells transfected with Ad-Foxa1 or Ad-Control.
2011-07-07 | GSE30447 | GEO
Project description:Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of liver diseases in the world. At present, the pathogenesis of NAFLD is not completely clear, and the regulatory role of inflammatory corpuscles in NAFLD-related metabolic diseases is increasingly prominent. NLRP6 is a member of the NLRs family of pattern recognition receptors and is related to the occurrence and development of NAFLD, but the specific mechanism is still unclear. We report here that NLRP6 is an important regulator of liver lipid metabolism, and its absence will affect the formation and accumulation of lipid droplets in the liver. In the HFD-induced NAFLD model group, NLRP6 deletion increased the mouse lipid content and aggravated hepatocyte steatosis by up-regulating the expressions of ADRP and CIDEC and down-regulating the expression of ApoB100.On the contrary, overexpression of NLRP6 in hepatocytes can significantly reduce intracellular lipid content and lipid droplets, and reduce the expression of ADRP and CIDEC. Indicated that NLRP6 can inhibit the accumulation of lipid droplets in hepatocytes by regulating the expression of ADRP, CIDEC and ApoB100, and thus alleviating the symptoms of NAFLD.
2024-01-31 | GSE239747 | GEO
Project description:Both adipocytes and hepatocytes have the capacity to store fat, but the factor(s) that determine fat distribution between these cell types remain unknown. In mice fed a high-fat diet, fat initially accumulates predominantly in adipocytes, while hepatic fat accumulation mainly emerges after the onset of epididymal adipocyte death that results in elevated free fatty acids to promote lipid accumulation in hepatocytes. However, it remains unclear whether other signals following adipocyte death are required to direct and/or promote hepatocytes to store fat and subsequently trigger metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease). Using genetically modified mouse models combined with bulk and single-cell RNA sequencing analysis, we demonstrated that adipocyte death induces an accumulation of S100A8+ macrophages in the liver, which is partially induced by fatty acids. Macrophage-specific deletion of the S100a8 gene reduced hepatic fat accumulation and MASLD severity in mice. Mechanistically, S100A8+ macrophages suppress cellular communication network factor (CCN3), a negative regulator of CD36, thereby enhancing CD36 expression in hepatocytes. In conclusion, adipocyte death promotes hepatic infiltration of S100A8+ macrophages, which drive hepatocyte lipid storage and subsequently promote MASLD progression through CD36 upregulation, partially mediated by CCN3 suppression.
2025-08-07 | GSE285615 | GEO
Project description:Both adipocytes and hepatocytes have the capacity to store fat, but the factor(s) that determine fat distribution between these cell types remain unknown. In mice fed a high-fat diet, fat initially accumulates predominantly in adipocytes, while hepatic fat accumulation mainly emerges after the onset of epididymal adipocyte death that results in elevated free fatty acids to promote lipid accumulation in hepatocytes. However, it remains unclear whether other signals following adipocyte death are required to direct and/or promote hepatocytes to store fat and subsequently trigger metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease). Using genetically modified mouse models combined with bulk and single-cell RNA sequencing analysis, we demonstrated that adipocyte death induces an accumulation of S100A8+ macrophages in the liver, which is partially induced by fatty acids. Macrophage-specific deletion of the S100a8 gene reduced hepatic fat accumulation and MASLD severity in mice. Mechanistically, S100A8+ macrophages suppress cellular communication network factor (CCN3), a negative regulator of CD36, thereby enhancing CD36 expression in hepatocytes. In conclusion, adipocyte death promotes hepatic infiltration of S100A8+ macrophages, which drive hepatocyte lipid storage and subsequently promote MASLD progression through CD36 upregulation, partially mediated by CCN3 suppression.
2025-08-07 | GSE285614 | GEO