Activators of peroxisome proliferator-activated receptor-α induce the expression of the uncoupling protein-3 gene in skeletal muscle -: A potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth
Activators of peroxisome proliferator-activated receptor-α induce the expression of the uncoupling protein-3 gene in skeletal muscle -: A potential mechanism for the lipid intake-dependent activation of uncoupling protein-3 gene expression at birth
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DOI：
10.2337/diabetes.48.6.1217
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发表时间：
1999-06-01
期刊：
影响因子：
7.7
通讯作者：
Villarroya, F
中科院分区：
文献类型：
--
作者：
Brun, S;Carmona, MC;Villarroya, F
最近鉴定的解偶联蛋白-3（UCP-3）基因，预测编码解偶联蛋白家族的新成员，优先在骨骼肌中表达，并且与肥胖和2型糖尿病的表型相关。我们已经确定，在小鼠个体发育过程中，UCP-3基因的表达在出生后不久就在骨骼肌中启动。UCP-3基因表达的诱导依赖于哺乳的开始，特别是脂质摄入。用过氧化物酶体增殖物激活受体（PPARs）的激活剂如氯贝特、苯扎贝特或（4-氯-6-（2，3-二甲基苯胺）-嘧啶硫基）乙酸（WY 14，643）处理新生小鼠，模拟食物摄入对UCP-3基因表达的作用。PPAR-alpha WY 14，643的特异性配体以时间和剂量依赖性方式诱导UCP-3基因表达，而对PPAR-gamma特异的噻唑烷二酮BRL 49653则无影响。这些治疗不会改变循环游离脂肪酸。在发育过程中，骨骼肌表达组成型水平的PPAR-delta mRNA，而PPAR-gamma基因的表达是不可检测的。PPAR-gamma基因表达在肌肉中受到发育调控，因为它在出生时首次表达，就在UCP-3基因诱导发生之前。在不表达PPAR-a的早产儿骨骼肌中，WY 14，643对UCP-3基因表达的诱导受损。有人提出，UCP-3基因主要是由PPAR-alpha激活调节新生儿肌肉。
The recently identified uncoupling protein-3 (UCP-3) gene, predicted to encode a new member of the family of uncoupling proteins, is preferentially expressed in skeletal muscle and has been related to phenotypes of obesity and type 2 diabetes. We have established that during mouse ontogeny, the expression of the UCP-3 gene is switched on in skeletal muscle just after birth. The induction of UCP-3 gene expression is dependent on the initiation of suckling and particularly on lipid intake. Treatment of newborn mice with activators of peroxisome proliferator-activated receptors (PPARs), such as clofibrate, bezafibrate, or (4-chloro-6-(2,3-xylidine)-pirimidinylthio)acetic acid (WY 14,643), mimics the action of food intake on UCP-3 gene expression. The specific ligand of PPAR-alpha WY 14,643 induces UCP-3 gene expression in a time- and dose-dependent manner, whereas the thiazolidinedione BRL 49653, specific for PPAR-gamma, has no effect. These treatments act without altering circulating free fatty acids. During development, skeletal muscle expresses constitutive levels of PPAR-delta mRNA, whereas expression of the PPAR-gamma gene is undetectable. PPAR-gamma gene expression is developmentally regulated in muscle as it is first expressed at birth, just before UCP-3 gene induction occurs. The induction of UCP-3 gene expression by WY 14,643 is impaired in skeletal muscle of premature neonates, which do not express PPAR-a. It is proposed that the UCP-3 gene is predominantly regulated in neonatal muscle by PPAR-alpha activation.