Neuregulin 4 (Nrg4), a novel brown fat–enriched hormone, plays a key role in the modulation of glucose and lipid metabolism and energy balance. Recent data have demonstrated that the expression of Nrg4 is substantially down‐regulated in mouse and human obesity, making its regulatory aspect intriguing. Because of the close relationship between Nrg4, obesity, and associated metabolic diseases, this systematic review aimed to assess the association of Nrg4 with obesity and related metabolic disturbances, emphasizing its possible mechanisms of action in these disorders. We searched PubMed/Medline, ScienceDirect, Scopus, EMBASE, ProQuest, and Google Scholar up until June 2019. The evidence reviewed here indicates that Nrg4 may contribute to the prevention of obesity and related metabolic complications by elevating brown adipose tissue activity, increasing the expression of thermogenic markers, decreasing the expression of lipogenic/adipogenic genes, exacerbating white adipose tissue browning, increasing the number of brite/beige adipocytes, promoting hepatic fat oxidation and ketogenesis, inducing neurite outgrowth, enhancing blood vessels in adipose tissue, increasing the circulatory levels of healthy adipokines, and improving glucose homeostasis. Thus, Nrg4 appears to be a novel therapeutic strategy for the treatment of obesity and associated metabolic complications. However, prospective cohort studies are warranted to confirm these outcomes.

中文翻译：

---

系统评价神经调节蛋白4（一种棕色的富含脂肪的分泌因子）与肥胖症和相关代谢紊乱的关系。

神经调节蛋白4（Nrg4）是一种新型的富含棕色脂肪的激素，在调节葡萄糖和脂质代谢以及能量平衡中起着关键作用。最近的数据表明，Nrg4的表达在小鼠和人类肥胖症中显着下调，从而使其调控方面引起了人们的兴趣。由于Nrg4，肥胖症和相关代谢疾病之间的密切关系，本系统综述旨在评估Nrg4与肥胖症和相关代谢紊乱的关系，强调其在这些疾病中的可能作用机制。我们一直搜索到PubMed / Medline，ScienceDirect，Scopus，EMBASE，ProQuest和Google Scholar，直到2019年6月为止。此处审查的证据表明Nrg4可能通过提高棕色脂肪组织的活性来预防肥胖症和相关的代谢并发症，增加生热标记物的表达，减少脂生性/脂肪形成基因的表达，加剧白色脂肪组织褐变，增加脂肪/米色脂肪细胞的数量，促进肝脂肪氧化和生酮，诱导神经突向外生长，增强脂肪组织中的血管，增加健康脂肪因子的循环水平，并改善葡萄糖稳态。因此，Nrg4似乎是治疗肥胖症和相关代谢并发症的一种新型治疗策略。但是，有必要进行前瞻性队列研究来证实这些结果。诱导神经突增生，增强脂肪组织中的血管，增加健康脂肪因子的循环水平，并改善葡萄糖稳态。因此，Nrg4似乎是治疗肥胖症和相关代谢并发症的一种新型治疗策略。但是，有必要进行前瞻性队列研究来证实这些结果。诱导神经突增生，增强脂肪组织中的血管，增加健康脂肪因子的循环水平，并改善葡萄糖稳态。因此，Nrg4似乎是治疗肥胖症和相关代谢并发症的一种新型治疗策略。但是，有必要进行前瞻性队列研究来证实这些结果。