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The transcription factor Hepatocyte Nuclear Factor 4A acts in the intestine to promote white adipose tissue energy storage

ABSTRACT: The transcription factor Hepatocyte Nuclear Factor 4A acts in the intestine to promote white adipose tissue energy storage

PROVIDER: PRJNA783018 | ENA |

REPOSITORIES: ENA

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The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage.

Project description:The transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.

| S-EPMC8752770 | biostudies-literature

The transcription factor Hepatocyte Nuclear Factor 4A acts in the intestine to promote white adipose tissue energy storage

Project description:HNF4A is a transcription factor that controls metabolic features of several endodermal epithelia. Using an intestinal conditional mouse model, here we demonstrate that HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole body energy expenditure under diet-induced obesity (DIO). Deletion of intestinal HNF4A causes mice to become DIO-resistant with preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while reintroduction of a stabilized GIP analog rescues the DIO-resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole body lipid homeostasis and points to a novel non-cell-autonomous regulatory circuit for body fat management.

2021-12-21 | GSE189439 | GEO

Cold Storage of Rat Hepatocyte Spheroids

Project description:The purpose of this study was to optimize conditions for cold storage of rat hepatocyte spheroids without freezing. Rat hepatocytes were isolated by a two-step perfusion method; hepatocyte spheroids were formed during 48 h of rocked culture in serum-free medium (SFM). Spheroids were then maintained in rocked culture at 37°C (control condition) or cold stored at 4°C for 24 or 48 h in six different cold storage solutions: SFM alone; SFM + 1 mM deferoxamine (Def); SFM + 1 ?M cyclosporin A (CsA); SFM + 1 mM Def + 1 ?M CsA, University of Wisconsin (UW) solution alone, UW + 1 mM Def.

2015-05-14 | ST000167 | MetabolomicsWorkbench

Hepatocyte growth factor time course

Project description:Cultured Madin-Darby canine kidney (MDCK) cells treated with hepatocyte growth factor (HGF) for 0, 3 and 24 hours. Each time point in triplicate. Keywords: time-course

2003-11-04 | GSE578 | GEO

Quantitative Proteomics Identify a Novel DNA Repair-Dependent Role for Hepatocyte Nuclear Factor 4α

Project description:Hepatocyte nuclear factor 4 (HNF4) is a transcription factor that acts as a master regulator of genes in several endodermal-derived tissues, including the intestine in which it plays a central role during development and tumorigenesis. To better delineate the mechanisms by which HNF4 can interfere during these processes, we combined stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomics with immunoprecipitation of green fluorescent protein (GFP) as well as with proximity-dependent purification by the biotin ligase BirA, both fused to HNF4. Surprisingly, these analyses identified a significant enrichment of proteins falling into the DNA repair gene ontology term, a so far unidentified biological feature of this transcription factor. Several of these proteins including PARP1, RAD50 and DNA-PKcs were confirmed to interact with HNF4in colorectal cancer cell lines. During DNA damage response, HNF4 localized to double strand DNA breaks in these cells. HNF4was able to interfere functionally during non-homologous end-joining (NHEJ). Overall, these observations identify an unsuspected role for this transcription factor during the DNA damage response.

2019-11-12 | PXD008365 | Pride

Transcription profiling of human lymphatic endothelial cells treated with hepatocyte Growth Factor (HGF)

Project description:Effect of Hepatocyte Growth Factor (HGF) on lymphatic endothelial cells.

2005-02-01 | E-MEXP-256 | biostudies-arrayexpress

Effect of depletion of Drosophila Hepatocyte Nuclear Factor 4 (dHNF4) in enterocytes on gene expression in the adult midgut

Project description:The main objective of the sudy was to characterize the functions of Drosophila Hepatocyte Nuclear Factor 4 (dHNF4) in midgut enterocytes. For this, we expressed a UAS-dHNF4 RNAi transgene under the control of mex-GAL4, which is active specifically in midgut enterocytes. We then collected adult male midguts, extracted total RNA and performed mRNA-seq. Our data demonstrate that dHNF4 acts as a master regulator of intestinal lipid metabolism in Drosophila.

2024-09-05 | GSE271746 | GEO

Seasonal energy storage in aquifers of urban areas

Project description:Efficiency and reliability of energy systems in urban districts with seasonal energy storage in aquifers (Aquifer Thermal Energy Storage ATES Berlin)

| PRJEB24963 | ENA

Hepatocyte maturation

Project description:Hepatocyte maturation

| PRJNA369428 | ENA

Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha

Project description:Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha

| PRJNA354702 | ENA

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