Adipose tissue lipin-1 expression is correlated with peroxisome proliferator-activated receptor α gene expression and insulin sensitivity in healthy young men
Adipose tissue lipin-1 expression is correlated with peroxisome proliferator-activated receptor α gene expression and insulin sensitivity in healthy young men
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DOI：
10.1210/jc.2007-1535
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发表时间：
2008-01-01
影响因子：
5.8
通讯作者：
Reue, Karen
中科院分区：
文献类型：
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作者：
Donkor, Jimmy;Sparks, Lauren M.;Reue, Karen
背景：Lipin-1在脂肪细胞甘油三酯生物合成和基因表达调控中发挥作用，两者都可能影响代谢稳态。目的：我们的目标是确定脂肪组织Lipin-1表达水平的变化是否影响年轻健康受试者的胰岛素敏感性和基因表达。设计和对象：56名健康年轻男性(22.6+/-3.2岁；26.4+/-4.1 kg/m(2))采用正血糖-高胰岛素钳夹检测胰岛素敏感性，用间接量热法测定全身耗氧量和呼吸商。结果：在健康青年男性中，Lipin-1的表达与胰岛素敏感性(R(2)=0.22；P<；0.01)、胰岛素刺激呼吸商(R(2)=0.16；P<；0.01)、运动最大耗氧量(R(2)=0.16；P<；0.01)呈正相关。在人类和Lipin-1转基因小鼠中，Lipin-1mRNA水平也与涉及脂质氧化、摄取和脂解的基因的表达相关。Lipin-1与在脂肪酸氧化中起关键作用的核受体a(R(2)=0.74；P<；1×10(-7))的相关性最强。结论：健康青年受试者和小鼠脂肪组织中Lipin-1的表达水平与脂肪酸氧化基因的良好代谢和表达有关。
Context: Lipin-1 functions in adipocyte triglyceride biosynthesis and in the regulation of gene expression, both of which may influence metabolic homeostasis.Objective: Our objective was to determine whether variations in adipose tissue lipin-1 expression levels influence insulin sensitivity and gene expression in young healthy human subjects.Design and Subjects: In 56 healthy young men (22.6 +/- 3.2 yr; 26.4 +/- 4.1 kg/m(2)) we determined insulin sensitivity by a euglycemic-hyperinsulinemic clamp, and whole body oxygen consumption and respiratory quotient by indirect calorimetry. We performed gene expression analysis in adipose tissue samples from human subjects and from lipin-1 transgenic mice using quantitative RT-PCR.Results: In healthy young men, lipin-1 expression was positively correlated with insulin sensitivity (R(2) = 0.22; P < 0.01), insulin-stimulated respiratory quotient (R(2) = 0.16; P < 0.01), and maximal oxygen consumption during exercise (R(2) = 0.16; P < 0.01). Lipin-1 mRNA levels were also correlated with expression of genes involved in lipid oxidation, uptake, and lipolysis, both in humans and in lipin-1 transgenic mice. The strongest correlation occurred between lipin-1 and peroxisome proliferator-activated receptor a (R(2) = 0.74; P < 1 X 10(-7)), a nuclear receptor with a key role in fatty acid oxidation.Conclusion: Lipin-1 expression levels in adipose tissue of healthy young subjects and in mice are correlated with a favorable metabolic profile and expression of fatty acid oxidation genes.