Low density lipoprotein receptor-related protein 1 is upregulated in epicardial fat from type 2 diabetes mellitus patients and correlates with glucose and triglyceride plasma levels
Low density lipoprotein receptor-related protein 1 is upregulated in epicardial fat from type 2 diabetes mellitus patients and correlates with glucose and triglyceride plasma levels
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DOI：
10.1007/s00592-012-0436-8
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发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Llorente-Cortes, V.
中科院分区：
文献类型：
--
作者：
Nasarre, L.;Juan-Babot, O.;Llorente-Cortes, V.
脂蛋白受体表达在体内糖尿病模型中脂肪组织的病理生理学中起着至关重要的作用。然而，没有糖尿病患者的研究。本研究的目的是分析（a）与非糖尿病患者相比，2型糖尿病患者心外膜和皮下脂肪中低密度脂蛋白受体相关蛋白1（LRP 1）和极低密度脂蛋白受体（VLDLR）的表达，以及（B）这些受体的表达与血浆参数之间可能的相关性。脂肪组织活检样本来自心肺转流术开始前接受心脏手术的糖尿病患者（n = 54）和非糖尿病患者（n = 22）。通过实时定量PCR和蛋白质印迹分析分别在mRNA水平和蛋白质水平分析脂肪LRP 1和VLDLR的表达。脂肪样品也进行了脂质提取，脂肪胆固醇酯，甘油三酯和游离胆固醇含量进行了分析，通过薄层色谱法。与非糖尿病患者相比，糖尿病患者心外膜脂肪中LRP 1表达更高（mRNA 17.63 +/- A 11.37 vs 7.01 +/- A 4.86; P = 0.02;蛋白11.23 +/- A 7.23 vs 6.75 +/- A 5.02，P = 0.04）。糖尿病患者心外膜脂肪中VLDLR表达也较高，但仅在mRNA水平上（231.25 +/- A 207.57 vs 56.64 +/- A 45.64，P = 0.02）。与非糖尿病患者相比，糖尿病患者皮下脂肪中LRP 1或VLDLR的表达无差异。心外膜LRP 1和VLDLR mRNA过表达与血浆甘油三酯水平呈正相关（分别为R（2）= 0.50，P = 0.01和R（2）= 0.44，P = 0.03），心外膜LRP 1也与血浆葡萄糖水平相关（R（2）= 0.33，P = 0.03）。这些结果表明，某些脂蛋白受体（例如LRP 1和VLDLR表达）的心外膜过表达可能在与2型糖尿病相关的脂质代谢改变中发挥关键作用。
Lipoprotein receptor expression plays a crucial role in the pathophysiology of adipose tissue in in vivo models of diabetes. However, there are no studies in diabetic patients. The aims of this study were to analyze (a) low-density lipoprotein receptor-related protein 1 (LRP1) and very low-density lipoprotein receptor (VLDLR) expression in epicardial and subcutaneous fat from type 2 diabetes mellitus compared with nondiabetic patients and (b) the possible correlation between the expression of these receptors and plasmatic parameters. Adipose tissue biopsy samples were obtained from diabetic (n = 54) and nondiabetic patients (n = 22) undergoing cardiac surgery before the initiation of cardiopulmonary bypass. Adipose LRP1 and VLDLR expression was analyzed at mRNA level by real-time PCR and at protein level by Western blot analysis. Adipose samples were also subjected to lipid extraction, and fat cholesterol ester, triglyceride, and free cholesterol contents were analyzed by thin-layer chromatography. LRP1 expression was higher in epicardial fat from diabetic compared with nondiabetic patients (mRNA 17.63 +/- A 11.37 versus 7.01 +/- A 4.86; P = 0.02; protein 11.23 +/- A 7.23 versus 6.75 +/- A 5.02, P = 0.04). VLDLR expression was also higher in epicardial fat from diabetic patients but only at mRNA level (231.25 +/- A 207.57 versus 56.64 +/- A 45.64, P = 0.02). No differences were found in the expression of LRP1 or VLDLR in the subcutaneous fat from diabetic compared with nondiabetic patients. Epicardial LRP1 and VLDLR mRNA overexpression positively correlated with plasma triglyceride levels (R (2) = 0.50, P = 0.01 and R (2) = 0.44, P = 0.03, respectively) and epicardial LRP1 also correlated with plasma glucose levels (R (2) = 0.33, P = 0.03). These results suggest that epicardial overexpression of certain lipoprotein receptors such as LRP1 and VLDLR expression may play a key role in the alterations of lipid metabolism associated with type 2 diabetes mellitus.