Project description:Fenofibrate is a specific agonist of the nuclear receptor PPARa. To identify the gene expression under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice. There are 36 liver samples, each from an individual mouse. The samples are from Ppara liver KO (LKO), Ppara KO (KO), wild-type (WT) and liver WT (LWT) male mice of 14 week-old from the same genetic background (C57Bl/6J) treated with Fenofibrate (100 mg/kg/day) or vehicle (aqueous solution of gum Arabic 3%) by daily gavage for 10 days. n= 4 mice for LKO, LWT and WT genotypes treated with vehicle; n=3 for KO mice treated with vehicle; n=5 mice for LWT, LKO and KO genotypes treated with fenofibrate; n=4 WT mice treated with fenofibrate. All mice were sacrified at ZT14.
Project description:Fenofibrate is a specific agonist of the nuclear receptor PPARa. To identify the gene expression under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice.
Project description:If the function of the nuclear receptor PPARa is well-known during a prolongated fasting, its hepatic biological function during feeding and refeeding conditions still needs to be investigated. Moreover, in vivo data collected so far on PPARa function during fasting were obtained using the total Ppara KO transgenic mouse model. To identify genes whose expression is under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice under three nutritional challenges. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice fed ad libitum, fasted for 24 hours and refed. There are 52 liver samples, each from an individual mouse. The samples are from Ppara liver KO (LKO), Ppara KO (KO), wild-type (WT) and liver WT (LWT) male mice of 8 week-old from the same genetic background (C57Bl/6J) fed ad libitum, fasted for 24 hours, fasted for 24 hours and then refed 24 hours more with glucose added in water (200g/l). In fed condition (Fed), n= 3 mice for LKO, LWT genotypes, n= 5 for KO and n= 4 fot WT; in fasting condition (Fas), n=5 for LKO, LWT and WT genotypes and n= 3 for KO; in refeeding condition (Ref), n= 5 for LKO, KO and WT genotypes and n= 4 for LWT. All mice were sacrified at ZT14.
Project description:If the function of the nuclear receptor PPARa is well-known during a prolongated fasting, its hepatic biological function during feeding and refeeding conditions still needs to be investigated. Moreover, in vivo data collected so far on PPARa function during fasting were obtained using the total Ppara KO transgenic mouse model. To identify genes whose expression is under the strict dependence of hepatic PPARa activity, we generated a new mouse strain of PPARa-specific deletion in hepatocyte (albumin-Cre+/- Pparaflox/flox or LKO) and we compared them to total Ppara KO (KO), wild-type (WT) and liver WT (albumin-Cre-/- Pparaflox/flox or LWT) mice under three nutritional challenges. We used microarrays to detail the global programme of gene expression in liver of Ppara LKO, LWT, Ppara KO and WT male mice fed ad libitum, fasted for 24 hours and refed.
Project description:Global hepatic gene expression data from PPARa liver KO, PPARa liver WT, PPARaKO and WT male mice fed ad libitum, fasted for 24 hours and re-fed
Project description:Fenofibrate is a synthetic ligand for the nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha, but there are reports that fenofibrate affects endothelial cells in PPARa-independent manner. In order to identify PPARa-dependently and PPARa-independently regulated transcripts we generated microarray data from human endothelial cells treated with fenofibrate with and without siRNA-mediated knock-down of PPARa.
Project description:Fenofibrate is a synthetic ligand for the nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha, but there are reports that fenofibrate affects endothelial cells in PPARa-independent manner. In order to identify PPARa-dependently and PPARa-independently regulated transcripts we generated microarray data from human endothelial cells treated with fenofibrate with and without siRNA-mediated knock-down of PPARa.
Project description:Fenofibrate is a synthetic ligand for the nuclear receptor peroxisome proliferator-activated receptor (PPAR) alpha, but there are reports that fenofibrate affects endothelial cells in PPARa-independent manner. In order to identify PPARa-dependently and PPARa-independently regulated transcripts we generated microarray data from human endothelial cells treated with fenofibrate with and without siRNA-mediated knock-down of PPARa. In this study, we generated microarray data from human umbilical vein endothelial cells (HUVECs) treated with fenofibrate with pretreatment PPARa or control siRNA. There are four time points (4, 8, 12 and 18hours) (n=1 at each time point).
Project description:Recent transcriptomic analyses in vitro comparing the transcriptomic profile of the short-chain per- and polyfluoroalkyl substances (PFAS) HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate) to that of other chemicals with known MOAs add to the current weight of evidence supporting the peroxisome proliferator-activated receptor alpha (PPARa) activator-induced rodent hepatocarcinogenesis mode of action (MOA) for HFPO-DA-mediated liver effects in rodents. To further inform the MOA of HFPO-DA and evaluate the PPARa-dependence of HFPO-DA-mediated liver effects in vivo, phenotypic and transcriptomic responses in wild-type (WT) and PPARa knockout (KO) mice were investigated following short-term exposure to HFPO-DA or well-established agonists of PPAR (GW7647) and PPARg (rosiglitazone), or cytotoxic agent (acetaminophen [APAP]). Phenotypic and transcriptomic assessment of mouse livers demonstrated a general lack of response to HFPO-DA or GW7647 exposure in PPARa KO but not WT mice, whereas exposure to rosiglitazone or APAP elicited similar, if not greater phenotypic and transcriptomic responses in PPARa KO mice compared to WT mice. Dose-dependent increases in liver weight and increased karyomegaly and mitosis scores via histopathology, as well as increased transcriptomic signaling related to PPARa activation and cell proliferation were observed in HFPO-DA or GW7647-exposed WT mice. The consistent phenotypic and transcriptomic signaling patterns between HFPO-DA and GW7647 in WT mice, and the lack of changes in PPARα KO mice, provide further support that HFPO-DA-mediated liver effects in mice are PPARa-dependent and occur via the PPARa MOA. Thus, these adverse effects in mice are not appropriate for use as the basis of toxicity values for human health risk assessment.