Dietary fat interacts with QTLs controlling induction of Pgc-1α and Ucp1 during conversion of white to brown fat
Dietary fat interacts with QTLs controlling induction of Pgc-1α and Ucp1 during conversion of white to brown fat
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DOI：
10.1152/physiolgenomics.00057.2003
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发表时间：
2003-07-07
影响因子：
4.6
通讯作者：
Kozak, LP
中科院分区：
文献类型：
--
作者：
Coulter, AA;Bearden, CM;Kozak, LP
为了确定新的调控因子控制诱导棕色脂肪细胞特异性线粒体解偶联蛋白（Ucp 1）mRNA在腹膜后白色脂肪库，我们以前映射的数量性状位点（QTL），控制这一性状的染色体2，3，8，和19。由于过氧化物酶体增殖物激活剂受体-γ辅激活因子-1 α（PGC-1）调节Ucp 1和其他能量代谢基因，我们通过分析A/J和C57 BL/6 J品系小鼠的回交后代来评估控制Ucp 1 mRNA水平的QTL是否也调节PGC-1 α mRNA水平。结果表明，3号染色体上的一个位点协调了低脂肪饮食小鼠腹膜后脂肪中Pgc-1 α和Ucp 1的表达;然而，该位点对Pgc-1 α的影响消失了，高脂肪饮食小鼠Ucp 1和Pgc-1 α之间的显著相关性严重降低。位于5号染色体上的一个额外的QTL也已被确定为Ucp 1 mRNA水平的选择性调节。与高脂饮食对3号染色体QTL的影响类似，高脂饮食小鼠中5号染色体QTL的连锁也丢失。因此，膳食脂肪对控制白色脂肪中能量代谢的PGC-1 α调节途径具有深远的影响。在白色脂肪的棕色脂肪细胞中观察到Ucp 1和Pgc-1 α表达的等位基因变异，但在肩胛间棕色脂肪中没有观察到，这表明存在根本不同的调节机制来控制这些组织的产热能力。
To identify novel regulatory factors controlling induction of the brown adipocyte-specific mitochondrial uncoupling protein (Ucp1) mRNA in the retroperitoneal white fat depot, we previously mapped quantitative trait loci (QTLs) that control this trait to chromosomes 2, 3, 8, and 19. Since the peroxisome proliferator activator receptor-gamma coactivator-1alpha (PGC-1) regulates Ucp1 and other genes of energy metabolism, we have evaluated whether the QTLs controlling Ucp1 mRNA levels also modulate Pgc-1alpha mRNA levels by analysis of backcross progeny from the A/J and C57BL/6J strains of mice. The results indicate that a locus on chromosome 3 orchestrates expression of Pgc-1alpha and Ucp1 in retroperitoneal fat of mice fed a low-fat diet; however, the effect of this locus on Pgc-1alpha is lost, and a significant correlation between Ucp1 and Pgc-1alpha is severely reduced in mice fed a high-fat diet. An additional QTL located on chromosome 5 has also been identified for the selective regulation of Ucp1 mRNA levels. Similar to the effects of a high-fat diet on the chromosome 3 QTL, linkage of the chromosome 5 QTL is also lost in mice on a high-fat diet. Thus dietary fat has a profound influence on PGC-1alpha-regulated pathways controlling energy metabolism in white fat. The allelic variation observed in the regulation of Ucp1 and Pgc-1alpha expression in brown adipocytes of white fat but not interscapular brown fat suggests that fundamentally different regulatory mechanisms exist to control the thermogenic capacities of these tissues.