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CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα
CREB3L3 is involved in fatty acid oxidation and ketogenesis in a mutual manner with PPARα. To evaluate relative contribution, a combination of knockout and transgenic mice was investigated. On a ketogenic-diet (KD) that highlights capability of hepatic ketogenesis, Creb3l3(−/−) mice exhibited reduct...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159891/ https://www.ncbi.nlm.nih.gov/pubmed/27982131 http://dx.doi.org/10.1038/srep39182 |
Sumario: | CREB3L3 is involved in fatty acid oxidation and ketogenesis in a mutual manner with PPARα. To evaluate relative contribution, a combination of knockout and transgenic mice was investigated. On a ketogenic-diet (KD) that highlights capability of hepatic ketogenesis, Creb3l3(−/−) mice exhibited reduction of expression of genes for fatty oxidation and ketogenesis comparable to Ppara(−/−) mice. Most of the genes were further suppressed in double knockout mice indicating independent contribution of hepatic CREB3L3. During fasting, dependency of ketogenesis on CREB3L3 is lesser extents than Ppara(−/−) mice suggesting importance of adipose PPARα for supply of FFA and hyperlipidemia in Creb3l3(−/−) mice. In conclusion CREB3L3 plays a crucial role in hepatic adaptation to energy starvation via two pathways: direct related gene regulation and an auto-loop activation of PPARα. Furthermore, as KD-fed Creb3l3(−/−) mice exhibited severe fatty liver, activating inflammation, CREB3L3 could be a therapeutic target for NAFLD. |
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