イベント・セミナー
Roles of NR and GPCR network focusing on autophagy in liver diseases
講演者：Prof. Sang Geon KIM 所属：College of Pharmacy, Dongguk University-Seoul開催日：2023-04-14 10:00
終了日：2023-04-14 11:30
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下記のとおり、令和5年4月14日（金）午前10時より、Dongguk大学のKim教授のセミナーを開催いたします。
日 時：令和5年４月14日（金）10：00～11：30
開催場所：病院地区キャンパス 薬学部附設システム創薬リサーチセンター グリーンファルマ研究所402
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タイトル：Roles of
NR and GPCR network focusing on autophagy in liver diseases
演 者：Prof. Sang Geon KIM (College of
Pharmacy, Dongguk University-Seoul)
要 旨：
Autophagy is a catabolic process in which autophagosomes
are formed de novo to engulf cytosolic contents such as damaged organelles,
lipids, and proteins. Autophagy is essential for the maintenance of
intracellular homeostasis, and thus autophagy dysfunction is associated with
various liver diseases. Autophagy is suppressed in liver diseases
caused by excessive high fat intake, which leads to excessive liver fat
accumulation and accelerated disease progression. In fatty liver disease, ATG4B
and Rab8b regulate different stages of the autophagy flux. ATG4B is involved in
the initiation phase, processing LC3, whereas Rab8b causes fusion of
autophagosome with the lysosome in the maturation phase. Previsously, we have
shown that LXRα induces the
accumulation of lipids through induction of a number of lipogenic genes such as
SREBP1 and SCD1. In addition, chronic alcohol intake promotes fat accumulation in hepatocytes through
changes in fat metabolism. Especially, accumulating evidence suggests that
autophagy plays a role in the progression of ALD. Chronic alcohol abuse
suppresses autophagy, resulting in excessive lipid accumulation and damaged
mitochondria. Therefore, enhancing autophagy can attenuate ALD progression. In
this study, we found that repetitive alcohol
exposure caused AhR overexpression and activation, dysregulating
autophagy, as verified by hepatocyte-specific
Ahr knockout models. In RNA-seq and metabolomic analyses, alcohol
treatment led to the inhibition of AhR-dependent autophagy. Autophagy
dysregulation was mediated with a change in AMPKα
dephosphorylation. In lipidomics and mitochondrial assays, hepatocyte-specific
AhR ablation diminished triglyceride and glycerophospholipid accumulation by
facilitating autophagy-dependent fuel burning and oxygen consumption. Our
results identify a new metabotropic mechanism by which AhR regulates autophagy
and lipid catabolism during
alcoholic liver disease exacerbation.
連絡先：大学院薬学研究院 生理学分野 加藤
TEL: 092-642-6668
E-mail : yu-kato@phar.kyushuu-u.ac.jp