目的：探讨新诊断2型糖尿病（T2DM）患者β抑制素2（β－arrestin 2）与脂肪甘油三酯脂酶（ATGL）水平变化及二者间相互关系及与胰岛素抵抗（ IR）的关系。方法选取2014－01～2014－06间牡丹江医学院第二附属医院内分泌科新诊断2型糖尿...目的：探讨新诊断2型糖尿病（T2DM）患者β抑制素2（β－arrestin 2）与脂肪甘油三酯脂酶（ATGL）水平变化及二者间相互关系及与胰岛素抵抗（ IR）的关系。方法选取2014－01～2014－06间牡丹江医学院第二附属医院内分泌科新诊断2型糖尿病患者60例为T2 DM组，同时选取该院同期健康体检者25例为正常对照（ NC）组。检测两组的一般状况，空腹血清β抑制素2、脂肪甘油三酯脂酶水平及其他相关生化指标，计算胰岛素抵抗指数（ HOMA－IR）。采用pearson线性相关分析和多元逐步回归分析血清β抑制素2、脂肪甘油三酯脂酶之间的相关性及二者与IR的关系。结果 NC组与T2 DM组的年龄、身高、SBP、BMI比较，差异无统计学意义（ P ＞0.05）。单因素分析显示，血浆ATGL与体重、BMI、SBP、DBP、LDL、TG、HBA1c、FPG、FINS、HOMA－IR均呈负相关（ P ＜0.05），与β抑制素2呈正相关（ P ＜0.05）；β抑制素2与体重、BMI、SBP、DBP、LDL、FPG、FINS、HOMA－IR均呈负相关（P＜0.05），与ATGL呈正相关（ P ＜0.05）。多元逐步回归分析提示，HOMA－IR为ATGL独立危险因素，HOMA－IR、HDL、HBA1c为β抑制素2独立危险因素，且HOMA－IR为影响ATGL及β抑制素2的最显著的因素。结论血ATGL及β抑制素2在2型糖尿病的发生及胰岛素抵抗形成中，发挥重要的作用。通过调节AT-GL、β抑制素2的表达水平可能减轻胰岛素抵抗，可能成为2型糖尿病治疗的新方向。展开更多
Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is one of the commonest causes of liver dysfunction.Adipose triglyceride lipase(ATGL)is closely related to lipid turnover and hepatic steatos...Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is one of the commonest causes of liver dysfunction.Adipose triglyceride lipase(ATGL)is closely related to lipid turnover and hepatic steatosis as the speed-limited triacylglycerol lipase in liver lipolysis.However,the expression and regulation of ATGL in NAFLD remain unclear.Herein,our results showed that ATGL protein levels were decreased in the liver tissues of high-fat diet(HFD)-fed mice,naturally obese mice,and cholangioma/hepatic carcinoma patients with hepatic steatosis,as well as in the oleic acid-induced hepatic steatosis cell model,while ATGL mRNA levels were not changed.ATGL protein was mainly degraded through the proteasome pathway in hepatocytes.Beta-transducin repeat containing(BTRC)was upregulated and negatively correlated with the decreased ATGL level in these hepatic steatosis models.Consequently,BTRC was identified as the E3 ligase for ATGL through predominant ubiquitination at the lysine 135 residue.Moreover,adenovirus-mediated knockdown of BTRC ameliorated steatosis in HFD-fed mouse livers and oleic acid-treated liver cells via upregulating the ATGL level.Taken together,BTRC plays a crucial role in hepatic steatosis as a new ATGL E3 ligase and may serve as a potential therapeutic target for treating NAFLD.展开更多
文摘目的：探讨新诊断2型糖尿病（T2DM）患者β抑制素2（β－arrestin 2）与脂肪甘油三酯脂酶（ATGL）水平变化及二者间相互关系及与胰岛素抵抗（ IR）的关系。方法选取2014－01～2014－06间牡丹江医学院第二附属医院内分泌科新诊断2型糖尿病患者60例为T2 DM组，同时选取该院同期健康体检者25例为正常对照（ NC）组。检测两组的一般状况，空腹血清β抑制素2、脂肪甘油三酯脂酶水平及其他相关生化指标，计算胰岛素抵抗指数（ HOMA－IR）。采用pearson线性相关分析和多元逐步回归分析血清β抑制素2、脂肪甘油三酯脂酶之间的相关性及二者与IR的关系。结果 NC组与T2 DM组的年龄、身高、SBP、BMI比较，差异无统计学意义（ P ＞0.05）。单因素分析显示，血浆ATGL与体重、BMI、SBP、DBP、LDL、TG、HBA1c、FPG、FINS、HOMA－IR均呈负相关（ P ＜0.05），与β抑制素2呈正相关（ P ＜0.05）；β抑制素2与体重、BMI、SBP、DBP、LDL、FPG、FINS、HOMA－IR均呈负相关（P＜0.05），与ATGL呈正相关（ P ＜0.05）。多元逐步回归分析提示，HOMA－IR为ATGL独立危险因素，HOMA－IR、HDL、HBA1c为β抑制素2独立危险因素，且HOMA－IR为影响ATGL及β抑制素2的最显著的因素。结论血ATGL及β抑制素2在2型糖尿病的发生及胰岛素抵抗形成中，发挥重要的作用。通过调节AT-GL、β抑制素2的表达水平可能减轻胰岛素抵抗，可能成为2型糖尿病治疗的新方向。
基金supported by grants from the National Natural Science Foundation of China(82070888,82070882,82100917,82273116,82203661,81901557,and 81902693)the National Key R&D Program of China(2018YFA0800403)+3 种基金Guangdong Special Support Program for Young Top Scientist(201629046)Guangdong Natural Science Fund(2021A1515010434,2022A1515012423,2022A1515012513,and 2023A1515010316)the Key Sci-Tech Research Project of Guangzhou Municipality(202201010820)China Postdoctoral Science Foundation(2021M703679 and 2020M683110).
文摘Non-alcoholic fatty liver disease(NAFLD),characterized by hepatic steatosis,is one of the commonest causes of liver dysfunction.Adipose triglyceride lipase(ATGL)is closely related to lipid turnover and hepatic steatosis as the speed-limited triacylglycerol lipase in liver lipolysis.However,the expression and regulation of ATGL in NAFLD remain unclear.Herein,our results showed that ATGL protein levels were decreased in the liver tissues of high-fat diet(HFD)-fed mice,naturally obese mice,and cholangioma/hepatic carcinoma patients with hepatic steatosis,as well as in the oleic acid-induced hepatic steatosis cell model,while ATGL mRNA levels were not changed.ATGL protein was mainly degraded through the proteasome pathway in hepatocytes.Beta-transducin repeat containing(BTRC)was upregulated and negatively correlated with the decreased ATGL level in these hepatic steatosis models.Consequently,BTRC was identified as the E3 ligase for ATGL through predominant ubiquitination at the lysine 135 residue.Moreover,adenovirus-mediated knockdown of BTRC ameliorated steatosis in HFD-fed mouse livers and oleic acid-treated liver cells via upregulating the ATGL level.Taken together,BTRC plays a crucial role in hepatic steatosis as a new ATGL E3 ligase and may serve as a potential therapeutic target for treating NAFLD.
