Increased browning of white adipocytes (beiging) is considered a promising therapeutic strategy to fight obesity and its associated metabolic complications. However, the molecular mechanism modulating brown and beige fat-mediated thermogenesis is not fully elucidated. Here, we identified the lymphocyte cytosolic protein 1 (LCP1) as a factor that obstructs fat browning in white adipocytes. LCP1 plays a vital role in non-hematopoietic malignancies, and is also a well-known tumor biomarker; however, evidence regarding its function in adipocytes remains to be elucidated. The current study explores the physiological role of LCP1 in cultured 3T3-L1 white adipocytes, by applying the loss-of-function study using siRNA. Induction of fat browning by LCP1 depletion was evidenced by evaluating the gene and protein expression levels of brown fat-associated markers through real-time qRT-PCR and immunoblot analysis, respectively. We observed that deficiency of LCP1 promotes mitochondrial biogenesis, and significantly enhances expressions of the core brown fat-specific genes (Cd137, Cidea, Cited1, Tbx1, and Tmem26) and proteins (PGC-1α, PRDM16, and UCP1). In addition, deficiency of LCP1 promotes lipid catabolism as well as suppresses adipogenesis and lipogenesis. Loss of LCP1 also ameliorates cellular stress by downregulating JNK and c-JUN in adipocytes, and stimulates apoptosis. A mechanistic study revealed that deficiency of LCP1 induces browning in white adipocytes, independently via β3-AR and the ERK signaling pathway. The current data reveals a previously unknown mechanism of LCP1 in browning of white adipocytes, and highlights the potential of LCP1 as a pharmacotherapeutic target for treating obesity and other metabolic disorders.

白色脂肪细胞（beiging）褐变增加被认为是对抗肥胖及其相关代谢并发症的一种有前途的治疗策略。然而，调节棕色和米色脂肪介导的产热的分子机制尚未完全阐明。在这里，我们将淋巴细胞胞质蛋白 1 (LCP1) 鉴定为阻碍白色脂肪细胞脂肪褐变的因素。LCP1在非造血系统恶性肿瘤中起着至关重要的作用，也是众所周知的肿瘤生物标志物；然而，关于其在脂肪细胞中的功能的证据仍有待阐明。目前的研究通过应用使用 siRNA 的功能丧失研究来探索 LCP1 在培养的 3T3-L1 白色脂肪细胞中的生理作用。通过分别通过实时 qRT-PCR 和免疫印迹分析评估棕色脂肪相关标志物的基因和蛋白质表达水平，证明了 LCP1 消耗诱导脂肪褐变。我们观察到 LCP1 的缺乏促进线粒体生物发生，并显着增强核心棕色脂肪特异性基因的表达。Cd137、Cidea、Cited1、Tbx1和Tmem26）和蛋白质（PGC-1α、PRDM16 和 UCP1）。此外，LCP1 的缺乏促进脂质分解代谢以及抑制脂肪生成和脂肪生成。LCP1 的缺失还通过下调脂肪细胞中的 JNK 和 c-JUN 来改善细胞应激，并刺激细胞凋亡。一项机制研究表明，LCP1 的缺乏独立通过β3-AR 和 ERK 信号通路诱导白色脂肪细胞褐变。目前的数据揭示了 LCP1 在白色脂肪细胞褐变中的一种以前未知的机制，并突出了 LCP1 作为治疗肥胖和其他代谢紊乱的药物治疗靶点的潜力。