Dataset Information

Transcriptional profiling of PPAR?-/- and CREB3L3-/- livers reveals disparate regulation of hepatoproliferative and metabolic functions of PPAR?.

ABSTRACT: BACKGROUND:Peroxisome Proliferator-Activated receptor ? (PPAR?) and cAMP-Responsive Element Binding Protein 3-Like 3 (CREB3L3) are transcription factors involved in the regulation of lipid metabolism in the liver. The aim of the present study was to characterize the interrelationship between PPAR? and CREB3L3 in regulating hepatic gene expression. Male wild-type, PPAR?-/-, CREB3L3-/- and combined PPAR?/CREB3L3-/- mice were subjected to a 16-h fast or 4?days of ketogenic diet. Whole genome expression analysis was performed on liver samples. RESULTS:Under conditions of overnight fasting, the effects of PPAR? ablation and CREB3L3 ablation on plasma triglyceride, plasma ?-hydroxybutyrate, and hepatic gene expression were largely disparate, and showed only limited interdependence. Gene and pathway analysis underscored the importance of CREB3L3 in regulating (apo)lipoprotein metabolism, and of PPAR? as master regulator of intracellular lipid metabolism. A small number of genes, including Fgf21 and Mfsd2a, were under dual control of PPAR? and CREB3L3. By contrast, a strong interaction between PPAR? and CREB3L3 ablation was observed during ketogenic diet feeding. Specifically, the pronounced effects of CREB3L3 ablation on liver damage and hepatic gene expression during ketogenic diet were almost completely abolished by the simultaneous ablation of PPAR?. Loss of CREB3L3 influenced PPAR? signalling in two major ways. Firstly, it reduced expression of PPAR? and its target genes involved in fatty acid oxidation and ketogenesis. In stark contrast, the hepatoproliferative function of PPAR? was markedly activated by loss of CREB3L3. CONCLUSIONS:These data indicate that CREB3L3 ablation uncouples the hepatoproliferative and lipid metabolic effects of PPAR?. Overall, except for the shared regulation of a very limited number of genes, the roles of PPAR? and CREB3L3 in hepatic lipid metabolism are clearly distinct and are highly dependent on dietary status.

SUBMITTER: Ruppert PMM

PROVIDER: S-EPMC6416987 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Transcriptional profiling of PPARα-/- and CREB3L3-/- livers reveals disparate regulation of hepatoproliferative and metabolic functions of PPARα.

Ruppert Philip M M PMM Park Jong-Gil JG Xu Xu X Hur Kyu Yeon KY Lee Ann-Hwee AH Kersten Sander S

BMC genomics 20190311 1

<h4>Background</h4>Peroxisome Proliferator-Activated receptor α (PPARα) and cAMP-Responsive Element Binding Protein 3-Like 3 (CREB3L3) are transcription factors involved in the regulation of lipid metabolism in the liver. The aim of the present study was to characterize the interrelationship between PPARα and CREB3L3 in regulating hepatic gene expression. Male wild-type, PPARα-/-, CREB3L3-/- and combined PPARα/CREB3L3-/- mice were subjected to a 16-h fast or 4 days of ketogenic diet. Whole genom ...[more]

PMID: 30866796

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Dataset Information

Transcriptional profiling of PPAR?-/- and CREB3L3-/- livers reveals disparate regulation of hepatoproliferative and metabolic functions of PPAR?.

Publications

Transcriptional profiling of PPARα-/- and CREB3L3-/- livers reveals disparate regulation of hepatoproliferative and metabolic functions of PPARα.

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