Cargando…
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: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782481842234982400 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Nakagawa, Yoshimi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5159891 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51598912016-12-21 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 Sci Rep Article 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. Nature Publishing Group 2016-12-16 /pmc/articles/PMC5159891/ /pubmed/27982131 http://dx.doi.org/10.1038/srep39182 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article 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 CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα |
title | CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα |
title_full | CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα |
title_fullStr | CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα |
title_full_unstemmed | CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα |
title_short | CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα |
title_sort | creb3l3 controls fatty acid oxidation and ketogenesis in synergy with pparα |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159891/ https://www.ncbi.nlm.nih.gov/pubmed/27982131 http://dx.doi.org/10.1038/srep39182 |
work_keys_str_mv | AT nakagawayoshimi creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT satohaoi creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT tezukahitomi creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT hansongiee creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT takeikenta creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT iwasakihitoshi creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT yatohshigeru creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT yahaginaoya creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT suzukihiroaki creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT iwasakiyasumasa creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT sonehirohito creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT matsuzakatakashi creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT yamadanobuhiro creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara AT shimanohitoshi creb3l3controlsfattyacidoxidationandketogenesisinsynergywithppara |