SND1 promotes cholesterol synthesis and ameliorates high fat diet-induced hepatic steatosis and insulin resistance in mice
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- 英文论文题名：SND1 promotes cholesterol synthesis and ameliorates high fat diet-induced hepatic steatosis and insulin resistance in mice
- 论文作者：Wang Xinting ; Lingbiao Xin ; Zhongchao Duan ; Zhiyu Zuo ; Ruanruan Ren ; Xin Liu ; Lin Ge ; Silvennoinen Olli ; Minxin Wei ; Zhi Yao ; Xi Yang ; Jie Yang
- 英文论文作者：Wang Xinting ; Lingbiao Xin ; Zhongchao Duan ; Zhiyu Zuo ; Ruanruan Ren ; Xin Liu ; Lin Ge ; Silvennoinen Olli ; Minxin Wei ; Zhi Yao ; Xi Yang ; Jie Yang ; Tianjin Medical University ; University of Tampere ; Tianjin Medical University General Hospital ; University of Manitoba
- 年：2016
- 作者机构：Tianjin Medical University;University of Tampere;Tianjin Medical University General Hospital;University of Manitoba;
- 英文论文关键词：NAFLD ; SREBP ; SCAP ; leptin ; insulin resistance ; phospholipids ; cholesterols
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R575.5
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：1290k
- 原文格式：D
- 会议级别：全国
摘要
Aim: Staphylococcal nuclease domain containing 1(SND1) transcriptionally activates adipogenesis and regulates adipocyte differentiation, but its contribution to the metabolic homeostasis in vivo is unclear. The current study aimed to explore impact of SND1 overexpression in vivo on high-fat diet-induced(HFD) nonalcoholic fatty liver disease(NAFLD).Method: Wild-type and globally expressed SND1 transgenic mice on C57BL/6 were fed a high-fat diet for 12 weeks.Results: Compared to wild-type mice, the HFD in transgenic mice induced lower liver and body weight as well as decreased hepatic steatosis and elevated hepatic cholesterol and LDL-cholesterol in the blood. Microarray profiling on HFD-liver revealed a series of genes involved in hepatic cholesterol biosynthesis were increased, which was associated with activation of sterol regulatory element-binding protein 2(SREBP2) through SREBP cleavage-activating protein(SCAP). In human hepatoma cells, chromatin immunoprecipitation assay revealed the binding of SND1 to the Scap promoter, and transient transfection with full length SND1 activated a Scap promoter-reporter in response to free fatty acids or TNFa, identifying Scap as a SND1 direct transcriptional target. Biopsy studies from NAFLD patients confirmed a significant correlation between SND1 and Scap mR NA expression in human liver tissues. Inflammation experiments showed an elevated inflammatory state in HFD-Tg liver with increased Tnfa expression. More importantly, HFD-transgenic mice show increased level of circulating leptin derived from larger white adipose mass characterized by active de novo lipogenesis in fat. Moreover, SND1 transgenic mice in high fat diet protected from insulin resistance, central to NAFLD pathogenesis, evidenced by increased insulin sensitivity both in mice liver and primary hepatocytes.Conclusions: SND1 regulates cholesterol metabolism and improve liver steatosis and insulin resistance in nonalcoholic fatty liver disease.
Aim: Staphylococcal nuclease domain containing 1(SND1) transcriptionally activates adipogenesis and regulates adipocyte differentiation, but its contribution to the metabolic homeostasis in vivo is unclear. The current study aimed to explore impact of SND1 overexpression in vivo on high-fat diet-induced(HFD) nonalcoholic fatty liver disease(NAFLD).Method: Wild-type and globally expressed SND1 transgenic mice on C57BL/6 were fed a high-fat diet for 12 weeks.Results: Compared to wild-type mice, the HFD in transgenic mice induced lower liver and body weight as well as decreased hepatic steatosis and elevated hepatic cholesterol and LDL-cholesterol in the blood. Microarray profiling on HFD-liver revealed a series of genes involved in hepatic cholesterol biosynthesis were increased, which was associated with activation of sterol regulatory element-binding protein 2(SREBP2) through SREBP cleavage-activating protein(SCAP). In human hepatoma cells, chromatin immunoprecipitation assay revealed the binding of SND1 to the Scap promoter, and transient transfection with full length SND1 activated a Scap promoter-reporter in response to free fatty acids or TNFa, identifying Scap as a SND1 direct transcriptional target. Biopsy studies from NAFLD patients confirmed a significant correlation between SND1 and Scap mR NA expression in human liver tissues. Inflammation experiments showed an elevated inflammatory state in HFD-Tg liver with increased Tnfa expression. More importantly, HFD-transgenic mice show increased level of circulating leptin derived from larger white adipose mass characterized by active de novo lipogenesis in fat. Moreover, SND1 transgenic mice in high fat diet protected from insulin resistance, central to NAFLD pathogenesis, evidenced by increased insulin sensitivity both in mice liver and primary hepatocytes.Conclusions: SND1 regulates cholesterol metabolism and improve liver steatosis and insulin resistance in nonalcoholic fatty liver disease.
Aim: Staphylococcal nuclease domain containing 1(SND1) transcriptionally activates adipogenesis and regulates adipocyte differentiation, but its contribution to the metabolic homeostasis in vivo is unclear. The current study aimed to explore impact of SND1 overexpression in vivo on high-fat diet-induced(HFD) nonalcoholic fatty liver disease(NAFLD).Method: Wild-type and globally expressed SND1 transgenic mice on C57BL/6 were fed a high-fat diet for 12 weeks.Results: Compared to wild-type mice, the HFD in transgenic mice induced lower liver and body weight as well as decreased hepatic steatosis and elevated hepatic cholesterol and LDL-cholesterol in the blood. Microarray profiling on HFD-liver revealed a series of genes involved in hepatic cholesterol biosynthesis were increased, which was associated with activation of sterol regulatory element-binding protein 2(SREBP2) through SREBP cleavage-activating protein(SCAP). In human hepatoma cells, chromatin immunoprecipitation assay revealed the binding of SND1 to the Scap promoter, and transient transfection with full length SND1 activated a Scap promoter-reporter in response to free fatty acids or TNFa, identifying Scap as a SND1 direct transcriptional target. Biopsy studies from NAFLD patients confirmed a significant correlation between SND1 and Scap mR NA expression in human liver tissues. Inflammation experiments showed an elevated inflammatory state in HFD-Tg liver with increased Tnfa expression. More importantly, HFD-transgenic mice show increased level of circulating leptin derived from larger white adipose mass characterized by active de novo lipogenesis in fat. Moreover, SND1 transgenic mice in high fat diet protected from insulin resistance, central to NAFLD pathogenesis, evidenced by increased insulin sensitivity both in mice liver and primary hepatocytes.Conclusions: SND1 regulates cholesterol metabolism and improve liver steatosis and insulin resistance in nonalcoholic fatty liver disease.
引文