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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...

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Detalles Bibliográficos
Autores principales: Nakagawa, Yoshimi, Satoh, Aoi, Tezuka, Hitomi, Han, Song-iee, Takei, Kenta, Iwasaki, Hitoshi, Yatoh, Shigeru, Yahagi, Naoya, Suzuki, Hiroaki, Iwasaki, Yasumasa, Sone, Hirohito, Matsuzaka, Takashi, Yamada, Nobuhiro, Shimano, Hitoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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
Descripción
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.