School of Pharmacy, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
Department of Biology, Georgia State University, Atlanta, Georgia.
Am J Physiol Endocrinol Metab. 2020 Apr 1;318(4):E453-E461. doi: 10.1152/ajpendo.00292.2019. Epub 2020 Jan 21.
Beige adipocytes have become a promising therapeutic target to combat obesity. Our senior author Dr. B. Xue previously discovered a transient but significant induction of beige adipocytes in mice during early postnatal development, which peaked at postnatal day (P) 20 and then disappeared thereafter. However, the physiological mechanism underlying the transient induction of the developmental beige cells remains mystery. Interestingly, there exists a postnatal surge of leptin in mice at P10 before the appearance of the developmental beige adipocytes. Given the neurotropic effect of leptin during neuronal development and its role in activating the sympathetic nervous system (SNS), we tested the hypothesis that postnatal leptin surge is required for the transient induction of developmental beige adipocytes through sympathetic innervation. Unlike wild-type (WT) mice that were able to acquire the developmentally induced beige adipocytes at P20, mice had much less uncoupling protein 1 (UCP1)-positive multilocular cells in inguinal white adipose tissue at the same age. This was consistent with reduced expression of UCP1 mRNA and protein levels in white fat of mice. In contrast, daily injection of mice with leptin between P8 and P16, mimicking the postnatal leptin surge, largely rescued the ability of these mice to acquire the developmentally induced beige adipocytes at P20, which was associated with enhanced sympathetic nerve innervation assessed by whole mount adipose tissue immunostaining of tyrosine hydroxylase. Our data demonstrate that the postnatal leptin surge is essential for the developmentally induced beige adipocyte formation in mice, possibly through increasing sympathetic nerve innervation.
米色脂肪细胞已成为治疗肥胖的有前途的治疗靶点。我们的资深作者 Xue 博士之前发现，在幼鼠出生后早期发育过程中，米色脂肪细胞会短暂但显著地诱导产生，在出生后第 20 天达到高峰，此后消失。然而，发育性米色细胞短暂诱导的生理机制仍然是个谜。有趣的是，在发育性米色脂肪细胞出现之前，幼鼠在出生后第 10 天存在瘦素的产后激增。鉴于瘦素在神经元发育过程中的神经营养作用及其在激活交感神经系统 (SNS) 中的作用，我们测试了以下假设：产后瘦素激增是通过交感神经支配来诱导发育性米色脂肪细胞短暂诱导的必要条件。与能够在第 20 天获得发育性诱导的米色脂肪细胞的野生型 (WT) 小鼠不同，在同一时期， 小鼠腹股沟白色脂肪组织中解偶联蛋白 1 (UCP1) 阳性多房细胞少得多。这与 小鼠白色脂肪中 UCP1 mRNA 和蛋白水平的表达降低一致。相比之下，在 P8 至 P16 期间每天给 小鼠注射瘦素，模拟产后瘦素激增，在很大程度上挽救了这些小鼠在第 20 天获得发育性诱导的米色脂肪细胞的能力，这与通过酪氨酸羟化酶的整个脂肪组织免疫染色评估交感神经支配增强有关。我们的数据表明，产后瘦素激增对于幼鼠发育性诱导的米色脂肪细胞形成是必不可少的，可能是通过增加交感神经支配。
