Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholestero...Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.展开更多
BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has...BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.展开更多
Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for is...Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for ischemic cardiovascular disease（CVD） and calcific aortic valve stenosis（CAVS）. The evidence for a causal role of Lp（a） in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp（a） as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp（a） functionality may be played by its oxidized phospholipids（OxPL） content. Importantly, most of circulating OxPL are associated with Lp（a）; however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp（a） over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp（a） is primarily driven by its OxPL content.An important role in Lp（a） functionality may be played by the lipoprotein-associated phospholipase A_2（Lp-PLA_2）,an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp（a）. The present review article discusses new data on the pathophysiological role of Lp（a） and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp（a）.展开更多
目的探讨绝经后2型糖尿病(type 2 diabetes,T2DM)患者血清残余脂蛋白胆固醇(residual lipoprotein cholesterol,RLP-C)与三酰甘油葡萄糖(triglyceride glucose,TyG)指数之间的相关性。方法选取2019年5月~2023年5月就诊于瑞丽市人民医院...目的探讨绝经后2型糖尿病(type 2 diabetes,T2DM)患者血清残余脂蛋白胆固醇(residual lipoprotein cholesterol,RLP-C)与三酰甘油葡萄糖(triglyceride glucose,TyG)指数之间的相关性。方法选取2019年5月~2023年5月就诊于瑞丽市人民医院的389例绝经后T2DM患者为研究对象,计算RLP-C和TyG指数,以TyG指数中位数(9.23)为界限将研究对象分为低TyG指数组(n=194)和高TyG指数组(n=195)。比较两组患者一般临床资料、代谢相关指标间的差异;相关性分析采用Spearman等级相关;影响因素分析采用单/多因素Logistic回归;诊断价值分析采用ROC曲线。结果与低TyG指数组相比,高TyG指数组患者高血压史(79.49%vs 70.62%)、高脂血症史占比(22.05%vs 13.40%)、血红蛋白(Hb)(120.34±19.96g/L vs 114.97±21.32g/L)、空腹血糖(FBG)[3.97(3.03,5.10)mmol/L vs 3.64(2.99,4.74)mmol/L]、总胆固醇(TC)[5.00(4.40,5.95)mmol/L vs 4.36(3.78,5.30)mmol/L]、三酰甘油(TG)[2.11(1.60,3.00)mmol/L vs 1.20(0.91,1.54)mmol/L]、低密度脂蛋白-胆固醇(LDL-C)[2.99(2.43,3.93)mmol/L vs 2.71(2.13,3.38)mmol/L]、非高密度脂蛋白-胆固醇(nonHDL-C)[3.94(3.22,4.82)mmol/L vs 3.15(2.53,3.94)mmol/L]、RLP-C浓度[0.76(0.52,1.08)mmol/L vs 0.44(0.29,0.59)mmol/L]升高,高密度脂蛋白-胆固醇(HDL-C)[1.08(0.91,1.25)mmol/L vs 1.17(1.00,1.43)mmol/L]浓度降低,差异具有统计学意义(χ^(2)=4.09,4.99;t=-2.56;Z=-2.34,-5.15,-12.08,-3.04,-6.23,-9.15,-3.99,均P<0.05)。Spearman相关性分析显示,总体而言,TyG与TC,TG,LDL-C,RLP-C,nonHDL-C呈显著正相关(r=0.304,0.769,0.179,0.386,0.571,均P<0.001),与HDL-C呈显著负相关(r=-0.306,P<0.001);在高TyG指数组中,TyG与TC,LDL-C之间相关性不具有统计学意义(均P>0.05)。单因素Logistic回归分析结果显示,高血压史、高脂血症、HDL-C,LDL-C和RLP-C是TyG水平的影响因素[OR(95%CI)=1.61(1.01~2.51),1.83(5.71~30.37),0.28(0.14~0.54),1.21(1.02~1.43),17.58(8.11~38.11),均P<0.05];多因素回归分析结果显示,仅RLP-C是TyG升高的独立危险因素[OR(95%CI)=13.17(5.71~30.37)P<0.001]。ROC曲线分析结果显示,RLP-C诊断TyG指数升高的曲线下面积(95%置信区间)[AUC(95%CI)]为0.768(95%CI:0.721~0.816),截断值为0.59mmol/L时,敏感度和特异度分别为69.71%和75.77%。结论RLP-C是绝经后T2DM患者TyG升高的独立危险因素,在预测胰岛素抵抗方面具有一定临床价值。展开更多
基金supported by the National Key R&D Program of China (2022YFE0196200)the National Natural Science Foundation of China–Deutsche Forschungsgemeinschaft of Germany (31761133021)+3 种基金the National Natural Science Foundation of China (31970469 and 31701794)the earmarked fund for Modern Agro-industry Technology Research System, China (2023CYJSTX01-20)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi, China (2017104)the Fund for Shanxi “1331 Project”, China
文摘Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.
基金Supported by the Xuanwu Hospital Capital Medical University Science Program for Fostering Young Scholars,No.YC20220113the Pilot Project for Public,No.Beijing Medical Research 2021-8.
文摘BACKGROUND Dyslipidemia and type 2 diabetes mellitus(T2DM)are chronic conditions with substantial public health implications.Effective management of lipid metabolism in patients with T2DM is critical.However,there has been insufficient attention given to the relationship between thyroid hormone sensitivity and dyslipidemia in the T2DM population,particularly concerning non-high-density lipoprotein cholesterol(non-HDL-C).AIM To clarify the association between thyroid hormone sensitivity and dyslipidemia in patients with T2DM.METHODS In this cross-sectional study,thyroid hormone sensitivity indices,the thyroid feedback quantile-based index(TFQI),the thyroid-stimulating hormone index(TSHI),the thyrotrophic T4 resistance index(TT4RI),and the free triiodothyronine(FT3)/free thyroxine(FT4)ratio were calculated.Logistic regression analysis was performed to determine the associations between those composite indices and non-HDL-C levels.Random forest variable importance and Shapley Additive Explanations(SHAP)summary plots were used to identify the strength and direction of the association between hyper-non-HDL-C and its major predictor.RESULTS Among the 994 participants,389(39.13%)had high non-HDL-C levels.Logistic regression analysis revealed that the risk of hyper-non-HDL-C was positively correlated with the TFQI(OR:1.584;95%CI:1.088-2.304;P=0.016),TSHI(OR:1.238;95%CI:1.034-1.482;P=0.02),and TT4RI(OR:1.075;95%CI:1.006-1.149;P=0.032)but was not significantly correlated with the FT3/FT4 ratio.The relationships between composite indices of the thyroid system and non-HDL-C levels differed according to sex.An increased risk of hyper-non-HDL-C was associated with elevated TSHI levels in men(OR:1.331;95%CI:1.003-1.766;P=0.048)but elevated TFQI levels in women(OR:2.337;95%CI:1.4-3.901;P=0.001).Among the analyzed variables,the average SHAP values were highest for TSHI,followed by TT4RI.CONCLUSION Impaired sensitivity to thyroid hormones was associated with high non-HDL-C levels in patients with T2DM.
文摘Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for ischemic cardiovascular disease（CVD） and calcific aortic valve stenosis（CAVS）. The evidence for a causal role of Lp（a） in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp（a） as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp（a） functionality may be played by its oxidized phospholipids（OxPL） content. Importantly, most of circulating OxPL are associated with Lp（a）; however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp（a） over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp（a） is primarily driven by its OxPL content.An important role in Lp（a） functionality may be played by the lipoprotein-associated phospholipase A_2（Lp-PLA_2）,an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp（a）. The present review article discusses new data on the pathophysiological role of Lp（a） and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp（a）.
文摘目的探讨绝经后2型糖尿病(type 2 diabetes,T2DM)患者血清残余脂蛋白胆固醇(residual lipoprotein cholesterol,RLP-C)与三酰甘油葡萄糖(triglyceride glucose,TyG)指数之间的相关性。方法选取2019年5月~2023年5月就诊于瑞丽市人民医院的389例绝经后T2DM患者为研究对象,计算RLP-C和TyG指数,以TyG指数中位数(9.23)为界限将研究对象分为低TyG指数组(n=194)和高TyG指数组(n=195)。比较两组患者一般临床资料、代谢相关指标间的差异;相关性分析采用Spearman等级相关;影响因素分析采用单/多因素Logistic回归;诊断价值分析采用ROC曲线。结果与低TyG指数组相比,高TyG指数组患者高血压史(79.49%vs 70.62%)、高脂血症史占比(22.05%vs 13.40%)、血红蛋白(Hb)(120.34±19.96g/L vs 114.97±21.32g/L)、空腹血糖(FBG)[3.97(3.03,5.10)mmol/L vs 3.64(2.99,4.74)mmol/L]、总胆固醇(TC)[5.00(4.40,5.95)mmol/L vs 4.36(3.78,5.30)mmol/L]、三酰甘油(TG)[2.11(1.60,3.00)mmol/L vs 1.20(0.91,1.54)mmol/L]、低密度脂蛋白-胆固醇(LDL-C)[2.99(2.43,3.93)mmol/L vs 2.71(2.13,3.38)mmol/L]、非高密度脂蛋白-胆固醇(nonHDL-C)[3.94(3.22,4.82)mmol/L vs 3.15(2.53,3.94)mmol/L]、RLP-C浓度[0.76(0.52,1.08)mmol/L vs 0.44(0.29,0.59)mmol/L]升高,高密度脂蛋白-胆固醇(HDL-C)[1.08(0.91,1.25)mmol/L vs 1.17(1.00,1.43)mmol/L]浓度降低,差异具有统计学意义(χ^(2)=4.09,4.99;t=-2.56;Z=-2.34,-5.15,-12.08,-3.04,-6.23,-9.15,-3.99,均P<0.05)。Spearman相关性分析显示,总体而言,TyG与TC,TG,LDL-C,RLP-C,nonHDL-C呈显著正相关(r=0.304,0.769,0.179,0.386,0.571,均P<0.001),与HDL-C呈显著负相关(r=-0.306,P<0.001);在高TyG指数组中,TyG与TC,LDL-C之间相关性不具有统计学意义(均P>0.05)。单因素Logistic回归分析结果显示,高血压史、高脂血症、HDL-C,LDL-C和RLP-C是TyG水平的影响因素[OR(95%CI)=1.61(1.01~2.51),1.83(5.71~30.37),0.28(0.14~0.54),1.21(1.02~1.43),17.58(8.11~38.11),均P<0.05];多因素回归分析结果显示,仅RLP-C是TyG升高的独立危险因素[OR(95%CI)=13.17(5.71~30.37)P<0.001]。ROC曲线分析结果显示,RLP-C诊断TyG指数升高的曲线下面积(95%置信区间)[AUC(95%CI)]为0.768(95%CI:0.721~0.816),截断值为0.59mmol/L时,敏感度和特异度分别为69.71%和75.77%。结论RLP-C是绝经后T2DM患者TyG升高的独立危险因素,在预测胰岛素抵抗方面具有一定临床价值。
