ArticleBMC genomics2019
Transcriptional profiling of PPARα-/- and CREB3L3-/- livers reveals disparate regulation of hepatoproliferative and metabolic functions of PPARα.
Article in BMC genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- The regulatory network of Mfsd2a in cerebral ischemia: a novel time-targeted intervention framework.Molecular biology reports · 2026Review
- Hepatic CB1 receptor signaling triggers GMetabolism: clinical and experimental · 2025Article
- Integrative Transcriptomic and Metabolomic Analysis of Muscle and Liver Reveals Key Molecular Pathways Influencing Growth Traits in Zhedong White Geese.Animals : an open access journal from MDPI · 2025Article
- Developmental programming: Sex-specific effects of prenatal exposure to a real-life mixture of environmental chemicals on liver function and transcriptome in sheep.Environmental pollution (Barking, Essex : 1987) · 2025Article
- The interplay between nutrigenomics and low-carbohydrate ketogenic diets in personalized healthcare.Frontiers in nutrition · 2025Review
- CREB3 protein family: the promising therapeutic targets for cardiovascular and metabolic diseases.Cell biology and toxicology · 2024Review
- Hepatic WDR23 proteostasis mediates insulin homeostasis by regulating insulin-degrading enzyme capacity.GeroScience · 2024Article
- Dietary medium-chain fatty acids reduce hepatic fat accumulation via activation of a CREBH-FGF21 axis.Molecular metabolism · 2024Article
- CAR memory-like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer.Science advances · 2024Article
- Disrupted Microbiota of Colon Results in Worse Immunity and Metabolism in Low-Birth-Weight Jinhua Newborn Piglets.Microorganisms · 2024Article
- Rab30 facilitates lipid homeostasis during fasting.Nature communications · 2024Article
- Fasting: From Physiology to Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Ketogenic Metabolic Therapy for Glioma.Cureus · 2022Article
- Peroxisome Proliferator-Activated Receptor Activation in Precision-Cut Bovine Liver Slices Reveals Novel Putative PPAR Targets in Periparturient Dairy Cows.Frontiers in veterinary science · 2022Article
- CREBH normalizes dyslipidemia and halts atherosclerosis in diabetes by decreasing circulating remnant lipoproteins.The Journal of clinical investigation · 2021Article
- Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges.International journal of molecular sciences · 2019Review
- CREB3 Transcription Factors: ER-Golgi Stress Transducers as Hubs for Cellular Homeostasis.Frontiers in cell and developmental biology · 2019Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPeroxisome 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 genome expression analysis was performed on liver samples.
resultsUnder conditions of overnight fasting, the effects of PPARα ablation and CREB3L3 ablation on plasma triglyceride, plasma β-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 PPARα as master regulator of intracellular lipid metabolism. A small number of genes, including Fgf21 and Mfsd2a, were under dual control of PPARα and CREB3L3. By contrast, a strong interaction between PPARα 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 PPARα. Loss of CREB3L3 influenced PPARα signalling in two major ways. Firstly, it reduced expression of PPARα and its target genes involved in fatty acid oxidation and ketogenesis. In stark contrast, the hepatoproliferative function of PPARα was markedly activated by loss of CREB3L3.
conclusionsThese data indicate that CREB3L3 ablation uncouples the hepatoproliferative and lipid metabolic effects of PPARα. Overall, except for the shared regulation of a very limited number of genes, the roles of PPARα and CREB3L3 in hepatic lipid metabolism are clearly distinct and are highly dependent on dietary status.
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