The PPARγ agonist rosiglitazone promotes the induction of brite adipocytes, increasing β-adrenoceptor-mediated mitochondrial function and glucose uptake
The PPARγ agonist rosiglitazone promotes the induction of brite adipocytes, increasing β-adrenoceptor-mediated mitochondrial function and glucose uptake
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PPARγ激动剂罗格列酮促进BRITE脂肪细胞的诱导，增加β-肾上腺素受体介导的线粒体功能和葡萄糖摄取
DOI：
10.1016/j.cellsig.2017.09.023
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发表时间：
2018-01-01
影响因子：
4.8
通讯作者：
Hutchinson, Dana S.
中科院分区：
文献类型：
--
作者：
Merlin, Jon;Sato, Masaaki;Hutchinson, Dana S.
布利特(或米色)脂肪细胞的募集和激活一直被认为是控制全身能量消耗的潜在途径。尽管大量研究表明棕色、棕色和白色脂肪细胞在基因和蛋白质标志物上存在差异，但关于这些棕色脂肪细胞的肾上腺素能调节和功能的信息很少。我们比较了来自三个不同部位的小鼠脂肪细胞的功能(循环AMP积累、耗氧率、线粒体功能、葡萄糖摄取、细胞外酸化率、钙内流)，这些脂肪细胞来自三个不同的储存库，即肩袖间棕色脂肪组织和腹股沟或附睾部白色脂肪组织，经过PPARγ激动剂罗格列酮慢性处理后。典型的棕色脂肪细胞容易表达β(3)-肾上腺素能受体，刺激β(3)-肾上腺素能受体可增加循环AMP蓄积、耗氧速率、线粒体功能、葡萄糖摄取和细胞外酸化速率。用罗格列酮处理棕色脂肪细胞可增加解偶联蛋白1(UCP1)水平，并增加β(3)-肾上腺素能受体线粒体功能，但不影响葡萄糖摄取反应。相比之下，罗格列酮治疗后，腹股沟白色脂肪细胞只表达UCP1和β(3)-肾上腺素能受体，这导致所有β(3)-肾上腺素能受体介导的功能增加。与腹股沟白色脂肪细胞相比，罗格列酮对附睾白色脂肪细胞的作用要低得多。罗格列酮还增加了α(1)肾上腺素受体介导的腹股沟和附睾白脂肪细胞钙内流和葡萄糖摄取(但不包括线粒体功能)的增加。总之，PPAR-γ激动剂罗格列酮可促进腹股沟和附睾白脂肪库培养的脆性脂肪细胞的诱导和功能。
Recruitment and activation of brite (or beige) adipocytes has been advocated as a potential avenue for manipulating whole-body energy expenditure. Despite numerous studies illustrating the differences in gene and protein markers between brown, brite and white adipocytes, there is very little information on the adrenergic regulation and function of these brite adipocytes. We have compared the functional (cyclic AMP accumulation, oxygen consumption rates, mitochondrial function, glucose uptake, extracellular acidification rates, calcium influx) profiles of mouse adipocytes cultured from three contrasting depots, namely interscapular brown adipose tissue, and inguinal or epididymal white adipose tissues, following chronic treatment with the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist rosiglitazone. Prototypical brown adipocytes readily express beta(3)-adrenoceptors, and beta(3)-adrenoceptor stimulation increases cyclic AMP accumulation, oxygen consumption rates, mitochondrial function, glucose uptake, and extracellular acidification rates. Treatment of brown adipocytes with rosiglitazone increases uncoupling protein 1 (UCP1) levels, and increases beta(3)-adrenoceptor mitochondrial function but does not affect glucose uptake responses. In contrast, inguinal white adipocytes only express UCP1 and beta(3)-adrenoceptors following rosiglitazone treatment, which results in an increase in all beta(3)-adrenoceptor-mediated functions. The effect of rosiglitazone in epididymal white adipocytes, was much lower compared to inguinal white adipocytes. Rosiglitazone also increased alpha(1)-adrenoceptor mediated increases in calcium influx and glucose uptake (but not mitochondrial function) in inguinal and epididymal white adipocytes. In conclusion, the PPAR gamma agonist rosiglitazone promotes the induction and function of brite adipocytes cultured from inguinal and epididymal white adipose depots.