Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease

ObjectiveTo establish a mouse model of hepatocyte-specific TM6SF2 knockout, and to investigate the role of TM6SF2 in the development of nonalcoholic fatty liver disease (NAFLD). MethodsThe CRISPR/Cas9 technique and the Cre/LoxP strategy were used to establish a stable mouse model of hepatocyte-speci...

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Autor principal:	ZHANG Jie
Formato:	article
Lenguaje:	ZH
Publicado:	Editorial Department of Journal of Clinical Hepatology 2021
Materias:	Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/4e7a05c4f9d44d5daeec0bea31f797ff
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spelling	oai:doaj.org-article:4e7a05c4f9d44d5daeec0bea31f797ff2021-11-17T11:06:43ZHepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease1001-5256https://doaj.org/article/4e7a05c4f9d44d5daeec0bea31f797ff2021-11-01T00:00:00Zhttp://www.lcgdbzz.org/cn/article/doi/10.3969/j.issn.1001-5256.2021.11.024https://doaj.org/toc/1001-5256ObjectiveTo establish a mouse model of hepatocyte-specific TM6SF2 knockout, and to investigate the role of TM6SF2 in the development of nonalcoholic fatty liver disease (NAFLD). MethodsThe CRISPR/Cas9 technique and the Cre/LoxP strategy were used to establish a stable mouse model of hepatocyte-specific TM6SF2 knockout. The mice with hepatocyte-specific TM6SF2 knockout and the control mice were given a normal diet or a high-fat diet (HFD) for 16 weeks, and related indices were measured, including general status (body weight and liver weight), glucose metabolic indices (fasting blood glucose and insulin), and lipid metabolism (plasma triglyceride, cholesterol, and liver triglyceride). The t-test was used for comparison of normally distributed continuous data between two groups. Results Under the condition of HFD, compared with the control mice, the mice with hepatocyte-specific TM6SF2 knockout had significantly higher liver weight (2.235±0.175 g vs 1.258±0.106 g, t=4.789, P＜0.01) and liver index (4.970%±0.298% vs 3.210%±0094%, t=5630, P＜0.01), and the loss of the TM6SF2 gene in hepatocytes aggravated the abnormal level of alanine aminotransferase induced by HFD (62.517±1.526 U/L vs 25.991±5.947 U/L, t=5.949, P＜0.01). Compared with the control mice under the condition of normal diet or HFD, the mice with TM6SF2 knockout had a significant increase in plasma insulin level (normal diet: 37.203±0.836 mIU/L vs 34.835±0.426 mIU/L, t=2.520, P=0.025; HFD: 41.093±1.226 mIU/L vs 35.817±0.500 mIU/L, t=3.985, P=0007), while there were no significant differences in the other indices associated with glucose metabolism (all P＞0.05). Under the condition of HFD, there were no significant differences in the levels of plasma triglyceride and cholesterol between the mice with hepatocyte-specific TM6SF2 knockout and the control group (P＞0.05), while the mice with hepatocyte-specific TM6SF2 knockout had a significant increase in thelevel of liver triglyceride compared with the control mice (23.969±0.978 mg/g vs 18.229±1.633 mg/g, t=3.015, P=0024). ConclusionHepatocyte-specific knockout of TM6SF2 can aggravate liver lipid accumulation and liver injury in mice with NAFLD. ZHANG JieEditorial Department of Journal of Clinical HepatologyarticleDiseases of the digestive system. GastroenterologyRC799-869ZHLinchuang Gandanbing Zazhi, Vol 37, Iss 11, Pp 2612-2616 (2021)
institution	DOAJ
collection	DOAJ
language	ZH
topic	Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	Diseases of the digestive system. Gastroenterology RC799-869 ZHANG Jie Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease
description	ObjectiveTo establish a mouse model of hepatocyte-specific TM6SF2 knockout, and to investigate the role of TM6SF2 in the development of nonalcoholic fatty liver disease (NAFLD). MethodsThe CRISPR/Cas9 technique and the Cre/LoxP strategy were used to establish a stable mouse model of hepatocyte-specific TM6SF2 knockout. The mice with hepatocyte-specific TM6SF2 knockout and the control mice were given a normal diet or a high-fat diet (HFD) for 16 weeks, and related indices were measured, including general status (body weight and liver weight), glucose metabolic indices (fasting blood glucose and insulin), and lipid metabolism (plasma triglyceride, cholesterol, and liver triglyceride). The t-test was used for comparison of normally distributed continuous data between two groups. Results Under the condition of HFD, compared with the control mice, the mice with hepatocyte-specific TM6SF2 knockout had significantly higher liver weight (2.235±0.175 g vs 1.258±0.106 g, t=4.789, P＜0.01) and liver index (4.970%±0.298% vs 3.210%±0094%, t=5630, P＜0.01), and the loss of the TM6SF2 gene in hepatocytes aggravated the abnormal level of alanine aminotransferase induced by HFD (62.517±1.526 U/L vs 25.991±5.947 U/L, t=5.949, P＜0.01). Compared with the control mice under the condition of normal diet or HFD, the mice with TM6SF2 knockout had a significant increase in plasma insulin level (normal diet: 37.203±0.836 mIU/L vs 34.835±0.426 mIU/L, t=2.520, P=0.025; HFD: 41.093±1.226 mIU/L vs 35.817±0.500 mIU/L, t=3.985, P=0007), while there were no significant differences in the other indices associated with glucose metabolism (all P＞0.05). Under the condition of HFD, there were no significant differences in the levels of plasma triglyceride and cholesterol between the mice with hepatocyte-specific TM6SF2 knockout and the control group (P＞0.05), while the mice with hepatocyte-specific TM6SF2 knockout had a significant increase in thelevel of liver triglyceride compared with the control mice (23.969±0.978 mg/g vs 18.229±1.633 mg/g, t=3.015, P=0024). ConclusionHepatocyte-specific knockout of TM6SF2 can aggravate liver lipid accumulation and liver injury in mice with NAFLD.
format	article
author	ZHANG Jie
author_facet	ZHANG Jie
author_sort	ZHANG Jie
title	Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease
title_short	Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease
title_full	Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease
title_fullStr	Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease
title_full_unstemmed	Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease
title_sort	hepatocyte-specific tm6sf2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease
publisher	Editorial Department of Journal of Clinical Hepatology
publishDate	2021
url	https://doaj.org/article/4e7a05c4f9d44d5daeec0bea31f797ff
work_keys_str_mv	AT zhangjie hepatocytespecifictm6sf2knockoutaggravateshepaticsteatosisinmicewithnonalcoholicfattyliverdisease
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Hepatocyte-specific TM6SF2 knockout aggravates hepatic steatosis in mice with nonalcoholic fatty liver disease

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