Active AKT2 stimulation of SREBP1/SCD1-mediated lipid metabolism boosts hepatosteatosis and cancer
Copyright © 2024. Published by Elsevier Inc..
Due to soared obesity population worldwide, hepatosteatosis is becoming a major risk factor for hepatocellular carcinoma (HCC). Undertaken molecular events during the progression of steatosis to liver cancer are thus under intensive investigation. In this study, we demonstrated that high-fat diet potentiated mouse liver AKT2. Hepatic AKT2 hyperactivation through gain-of-function mutation of Akt2 (Akt2E17K) caused spontaneous hepatosteatosis, injury, inflammation, fibrosis, and eventually HCC in mice. AKT2 activation also exacerbated lipopolysaccharide and D-galactosamine hydrochloride-induced injury/inflammation and N-Nitrosodiethylamine (DEN)-induced HCC. A positive correlation between AKT2 activity and SCD1 expression was observed in human HCC samples. Activated AKT2 enhanced the production of monounsaturated fatty acid which was dependent on SREBP1 upregulation of SCD1. Blockage of active SREBP1 and ablation of SCD1 reduced steatosis, inflammation, and tumor burden in DEN-treated Akt2E17K mice. Therefore, AKT2 activation is crucial for the development of steatosis-associated HCC which can be treated with blockage of AKT2-SREBP1-SCD1 signaling cascade.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:268 |
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| Enthalten in: |
Translational research : the journal of laboratory and clinical medicine - 268(2024) vom: 18. Jan., Seite 51-62 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huang, Fuqiang [VerfasserIn] |
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| Links: |
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| Themen: |
AKT2 |
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| Anmerkungen: |
Date Revised 28.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.trsl.2024.01.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2024. Published by Elsevier Inc. | ||
| 520 | |a Due to soared obesity population worldwide, hepatosteatosis is becoming a major risk factor for hepatocellular carcinoma (HCC). Undertaken molecular events during the progression of steatosis to liver cancer are thus under intensive investigation. In this study, we demonstrated that high-fat diet potentiated mouse liver AKT2. Hepatic AKT2 hyperactivation through gain-of-function mutation of Akt2 (Akt2E17K) caused spontaneous hepatosteatosis, injury, inflammation, fibrosis, and eventually HCC in mice. AKT2 activation also exacerbated lipopolysaccharide and D-galactosamine hydrochloride-induced injury/inflammation and N-Nitrosodiethylamine (DEN)-induced HCC. A positive correlation between AKT2 activity and SCD1 expression was observed in human HCC samples. Activated AKT2 enhanced the production of monounsaturated fatty acid which was dependent on SREBP1 upregulation of SCD1. Blockage of active SREBP1 and ablation of SCD1 reduced steatosis, inflammation, and tumor burden in DEN-treated Akt2E17K mice. Therefore, AKT2 activation is crucial for the development of steatosis-associated HCC which can be treated with blockage of AKT2-SREBP1-SCD1 signaling cascade | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AKT2 | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Hepatosteatosis | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Monounsaturated fatty acid | |
| 700 | 1 | |a Zhao, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Pei |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Mengjie |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Shuhui |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Bohao |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jingpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Gai, Xiaochen |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Yilei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lianmei |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zhongdong |e verfasserin |4 aut | |
| 700 | 1 | |a Zha, Xiaojun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Fangming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hongbing |e verfasserin |4 aut | |
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