論文

国際誌
2022年12月1日

Hepatocyte- or macrophage-specific SREBP-1a deficiency in mice exacerbates methionine- and choline-deficient diet-induced nonalcoholic fatty liver disease.

American journal of physiology. Gastrointestinal and liver physiology
  • Masaya Araki
  • Yoshimi Nakagawa
  • Hodaka Saito
  • Yasunari Yamada
  • Song-Iee Han
  • Yuhei Mizunoe
  • Hiroshi Ohno
  • Takafumi Miyamoto
  • Motohiro Sekiya
  • Takashi Matsuzaka
  • Hirohito Sone
  • Hitoshi Shimano
  • 全て表示

323
6
開始ページ
G627-G639
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1152/ajpgi.00090.2022

Sterol regulatory element-binding proteins (SREBPs) are master transcription factors for lipid synthesis, and SREBP-1 is important for fatty acid and triglyceride synthesis. SREBP-1 has two isoforms, SREBP-1a and SREBP-1c, which are splicing variants transcribed from the Srebf1 gene. Although SREBP-1a exhibits stronger transcriptional activity than SREBP-1c, hepatic SREBP-1c is considered more physiologically important. We generated SREBP-1a flox mice using the CRISPR/Cas9 system and hepatocyte- and macrophage-specific SREBP-1a knockout (KO) mice (LKO, liver-knockout; and mΦKO, macrophage-knockout). There were no significant differences among all the mouse genotypes upon feeding with a normal diet. However, feeding with a methionine- and choline-deficient (MCD) diet resulted in exacerbated liver injury in both KO mice. In LKO mice, fatty liver was unexpectedly exacerbated, leading to macrophage infiltration and inflammation. In contrast, in mΦKO mice, the fatty liver state was similar to that in flox mice, but the polarity of the macrophages in the liver was transformed into a proinflammatory M1 subtype, resulting in the exacerbation of inflammation. Taken together, we found that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in MCD diet-induced hepatitis.NEW & NOTEWORTHY Hepatocyte- and macrophage-specific SREBP-1a knockout mice were generated for the first time. This study reveals that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in methionine- and choline-deficient diet-induced hepatitis.

リンク情報
DOI
https://doi.org/10.1152/ajpgi.00090.2022
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/36283088
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000896018500008&DestApp=WOS_CPL
URL
https://publons.com/wos-op/publon/56910866/
ID情報
  • DOI : 10.1152/ajpgi.00090.2022
  • ORCIDのPut Code : 137935931
  • PubMed ID : 36283088
  • Web of Science ID : WOS:000896018500008

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