ASC-1 transporter-dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation
ASC-1 transporter-dependent amino acid uptake is required for the efficient thermogenic response of human adipocytes to adrenergic stimulation
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DOI：
10.1002/1873-3468.14155
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发表时间：
2021-07-23
期刊：
影响因子：
3.5
通讯作者：
Fesus, Laszlo
中科院分区：
文献类型：
--
作者：
Arianti, Rini;Vinnai, Boglarka Agnes;Fesus, Laszlo
棕色和米色脂肪细胞通过解偶联蛋白1（UCP 1）依赖性和UCP 1非依赖性产热来消耗能量，这可用于开发针对肥胖的治疗方法。我们已经发现，在人深颈棕色倾向和米色主管皮下颈祖细胞和SGBS前脂肪细胞的脂肪细胞分化过程中，丙氨酸/丝氨酸/半胱氨酸转运蛋白-1（ASC-1）的mRNA和蛋白质表达被诱导。分化脂肪细胞的cAMP刺激导致丝氨酸、半胱氨酸和甘氨酸摄取增加，同时伴随耗氧量增加、UCP 1依赖性质子泄漏增加、肌酸驱动的底物循环偶联呼吸增加以及产热标志物基因和几种呼吸复合物亚基上调;在存在特异性ASC-1抑制剂BMS-466442的情况下，这些结果受到阻碍。我们的数据表明，ASC-1依赖的丝氨酸，半胱氨酸和甘氨酸的消耗是必需的有效的产热刺激人脂肪细胞。
Brown and beige adipocytes dissipate energy by uncoupling protein 1 (UCP1)-dependent and UCP1-independent thermogenesis, which may be utilized to develop treatments against obesity. We have found that mRNA and protein expression of the alanine/serine/cysteine transporter-1 (ASC-1) was induced during adipocyte differentiation of human brown-prone deep neck and beige-competent subcutaneous neck progenitors, and SGBS preadipocytes. cAMP stimulation of differentiated adipocytes led to elevated uptake of serine, cysteine, and glycine, in parallel with increased oxygen consumption, augmented UCP1-dependent proton leak, increased creatine-driven substrate cycle-coupled respiration, and upregulation of thermogenesis marker genes and several respiratory complex subunits; these outcomes were impeded in the presence of the specific ASC-1 inhibitor, BMS-466442. Our data suggest that ASC-1-dependent consumption of serine, cysteine, and glycine is required for efficient thermogenic stimulation of human adipocytes.