Postnatal leptin surge is critical for the transient induction of the developmental beige adipocytes in mice

• Published in: American journal of physiology: endocrinology and metabolism 2020-04, Vol.318 (4), p.E453-E461
• Main Authors: Wu, Rui, Yu, Wenyan, Fu, Lizhi, Li, Fenfen, Jing, Jia, Cui, Xin, Wang, Shirong, Cao, Qiang, Xue, Bingzhong, Shi, Hang
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes, Beige - drug effects; Adipocytes, Beige - metabolism; Adipocytes, White - drug effects; Adipocytes, White - metabolism; Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - growth & development; Adipose Tissue - innervation; Aging; Animal models; Animals; Dose-Response Relationship, Drug; Female; Gene expression; Hydroxylase; Innervation; Leptin; Leptin - metabolism; Leptin - pharmacology; Male; Mice; Mice, Obese; Mimicry; mRNA; Proteins; Sympathetic nerves; Sympathetic Nervous System; Therapeutic applications; Tyrosine; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - metabolism; Uncoupling protein 1; Uncoupling Protein 1 - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00292.2019

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.