学術雑誌論文 CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα

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

6p.39182 , 2016-12 , Nature Publishing Group
ISSN:2045-2322
内容記述
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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