생명과학연구소 특별세미나_김승진 교수님(강원대)

일시: 2021. 11. 25 (목) 오후 5시

온라인: https://kangwon-ac-kr.zoom.us/j/81977781881?pwd=MUpvTVF5a0Npanc2K1FJa1d4OVJRQT09

Selection and Utilization of Mouse Models in Metabolic Diseases

김승진 교수(강원대학교)

The current presentation discusses mouse models which focus on metabolic diseases. Adipocyte death occurs under various pathophysiological conditions, including obesity and alcohol drinking, and can trigger organ damage particularly in the liver, but the underlying mechanisms remain obscure. To explore these mechanisms, we developed a mouse model of inducible adipocyte death by overexpressing the human CD59 (hCD59) on adipocytes (adipocyte-specific hCD59 transgenic mice). Injection of these mice with intermedilysin (ILY), which rapidly lyses hCD59 expressing cells exclusively by binding to the hCD59 but not mouse CD59, resulted in the acute selective death of adipocytes, adipose macrophage infiltration, and elevation of serum free fatty acid (FFA) levels. ILY injection also resulted in the secondary damage to multiple organs with the strongest injury observed in the liver, with inflammation and hepatic macrophage activation. Mechanistically, acute adipocyte death elevated epinephrine and norepinephrine levels and activated lipolysis pathways in adipose tissue in a chemokine (C-C motif) receptor 2-positive (CCR2+) macrophage-dependent manner, which was followed by FFA release and lipotoxicity in the liver. Additionally, acute adipocyte death caused hepatic CCR2+ macrophage activation and infiltration, further exacerbating liver injury. Our findings suggest that adipocyte death predominantly induces liver injury and inflammation, which is probably due to the superior sensitivity of hepatocytes to lipotoxicity and the abundance of macrophages in the liver.

학력 및 약력

2006        B.S. Biological Science, Chonnam National University

2008        M.S. Molecular Physiology, Chonnam National University

2013        Ph.D. Molecular Physiology, Chonnam National University

2014-2019   Post-doctoral fellow, National Institutes of Health, USA

2019-현재   Assistant Professor, Kangwon Instititute of Inclusive Technology (KIIT), Kangwon National University,

주요발표논문 (최근)

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2. Seung-Jin Kim, Dechun Feng, Adrien Guillot, Shen Dai, Fengming Liu, Seonghwan Hwang, Richard Parker, Wonhyo Seo, Yong He, Godlewski Grzegorz, Yuhong Lin, Won-Il Jeong, Xuebin Qin, George Kunos and Bin Gao. (2019) Adipocyte death preferentially induces liver injury and inflammation through the activation of chemokine (C-C Motif) receptor 2-positive macrophages and lipolysis. Hepatology 69(5), 1965-1982.

3. Richard Parker#, Seung-Jin Kim#(Co-first author), Gene Y Im, Jonathan Nahas, Balraj Dhesi, Nikhil Vergis, Ashish Sinha, Antonella Ghezzi, Marco Rink, Anne McCune, Guruprasad Aithal, Philip Newsome, Chris Weston, Andrew Holt and Bin Gao. (2019) Obesity increases morbidity and mortality in alcoholic hepatitis. EBioMedicine 45, 511-518 (# Contributed equally to this work).

4. Tyler J. Lahusen#, Seung-Jin Kim#(Co-first author), Kai Miao, Zebin Huang, Xiaoling Xu and Chu-Xia Deng. (2018) BRCA1 function in the intra-S checkpoint is activated by acetylation via a pCAF/SIRT1 axis. Oncogene 37(17), 2343-2350 (# Contributed equally to this work)

5. Richard Parker#, Seung-Jin Kim#(Co-first author), and Bin Gao. (2018) Alcohol, adipose tissue and liver disease: mechanistic links and clinical considerations. Nat. Rev. Gastroenterol. & Hepatol. 15, 50-59 (# Contributed equally to this work).