Hypoxia-inducible Lipid Droplet-associated (HILPDA) is a novel Peroxisome Proliferator-activated Receptor (PPAR) target involved in hepatic triglyceride secretion
Peroxisome proliferator-activated receptors (PPARs) play major roles in the regulation of hepatic lipid metabolism through the control of numerous genes involved in processes such as lipid uptake and fatty acid oxidation. Here we identify hypoxia-inducible lipid droplet-associated (Hilpda/Hig2) as a...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
May 29, 2014
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| In: |
The journal of biological chemistry
Year: 2014, Jahrgang: 289, Heft: 22, Pages: 19279-19293 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M114.570044 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://dx.doi.org/10.1074/jbc.M114.570044
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| Verfasserangaben: | Frits Mattijssen, Anastasia Georgiadi, Tresty Andasarie, Ewa Szalowska, Annika Zota, Anja Krones-Herzig, Christoph Heier, Dariusz Ratman, Karolien De Bosscher, Ling Qi, Rudolf Zechner, Stephan Herzig, and Sander Kersten |
| Zusammenfassung: | Peroxisome proliferator-activated receptors (PPARs) play major roles in the regulation of hepatic lipid metabolism through the control of numerous genes involved in processes such as lipid uptake and fatty acid oxidation. Here we identify hypoxia-inducible lipid droplet-associated (Hilpda/Hig2) as a novel PPAR target gene and demonstrate its involvement in hepatic lipid metabolism. Microarray analysis revealed that Hilpda is one of the most highly induced genes by the PPARα agonist Wy14643 in mouse precision cut liver slices. Induction of Hilpda mRNA by Wy14643 was confirmed in mouse and human hepatocytes. Oral dosing with Wy14643 similarly induced Hilpda mRNA levels in livers of wild-type mice but not Ppara−/− mice. Transactivation studies and chromatin immunoprecipitation showed that Hilpda is a direct PPARα target gene via a conserved PPAR response element located 1200 base pairs upstream of the transcription start site. Hepatic overexpression of HILPDA in mice via adeno-associated virus led to a 4-fold increase in liver triglyceride storage, without any changes in key genes involved in de novo lipogenesis, β-oxidation, or lipolysis. Moreover, intracellular lipase activity was not affected by HILPDA overexpression. Strikingly, HILPDA overexpression significantly impaired hepatic triglyceride secretion. Taken together, our data uncover HILPDA as a novel PPAR target that raises hepatic triglyceride storage via regulation of triglyceride secretion. |
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| Beschreibung: | Gesehen am 05.08.2020 |
| Beschreibung: | Online Resource |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M114.570044 |