Department of Pharmaceutical Sciences and Technology, Division of Pharmacology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India.
Curr Pharm Des. 2024;30(30):2387-2399. doi: 10.2174/0113816128318741240611114448.
Growth Differentiation Factor 15 (GDF15) has emerged as a pivotal signaling molecule implicated in diverse physiological processes, spanning metabolic regulation, inflammation, and cardiovascular health. This study provides a comprehensive exploration of GDF15's multifaceted role, primarily focusing on its association with obesity-related complications and therapeutic potential. GDF15's involvement in energy homeostasis, specifically its regulation of body weight and appetite through hindbrain neuron activation and the GFRAL-RET signaling pathway, underscores its significance as an appetite-regulating hormone. GDF15's intricate modulation within adipose tissue dynamics in response to dietary changes and obesity, coupled with its influence on insulin sensitivity, highlights its critical role in metabolic health. The manuscript delves into the intricate crosstalk between GDF15 and pathways related to insulin sensitivity, macrophage polarization, and adipose tissue function, elucidating its potential as a therapeutic target for metabolic disorders associated with obesity. GDF15's association with chronic low-grade inflammation and its impact on cardiovascular health, particularly during hyperlipidemia and ischemic events, are explored. The intricate relationship between GDF15 and cardiovascular diseases, including its effects on endothelial function, cardiac hypertrophy, and heart failure, emphasizes its multifaceted nature in maintaining overall cardiovascular well-being. Challenges regarding the therapeutic application of GDF15, such as long-term safety concerns and ongoing clinical investigations, are discussed. Lastly, future research directions exploring GDF15's potential in addressing obesity-related complications and cardiovascular risks are proposed, highlighting its promising role as a therapeutic target in reshaping treatment strategies for obesity and associated health conditions.
生长分化因子 15（GDF15）已成为一种关键的信号分子，涉及多种生理过程，包括代谢调节、炎症和心血管健康。本研究全面探讨了 GDF15 的多方面作用，主要集中在其与肥胖相关并发症的关联及其治疗潜力。GDF15 参与能量稳态，特别是通过后脑神经元激活和 GFRAL-RET 信号通路调节体重和食欲，突显了其作为一种食欲调节激素的重要性。GDF15 对饮食变化和肥胖引起的脂肪组织动态的复杂调节，以及其对胰岛素敏感性的影响，突出了其在代谢健康中的关键作用。本文深入研究了 GDF15 与胰岛素敏感性、巨噬细胞极化和脂肪组织功能相关途径之间的复杂相互作用，阐明了其作为与肥胖相关代谢紊乱治疗靶点的潜力。探讨了 GDF15 与慢性低度炎症之间的关联及其对心血管健康的影响，特别是在高血脂和缺血事件期间。GDF15 与心血管疾病之间的复杂关系，包括其对内皮功能、心肌肥大和心力衰竭的影响，强调了其在维持整体心血管健康方面的多方面性质。讨论了 GDF15 治疗应用面临的挑战，如长期安全性问题和正在进行的临床研究。最后，提出了探索 GDF15 在解决肥胖相关并发症和心血管风险方面的潜在作用的未来研究方向，强调了其作为治疗靶点在重塑肥胖及其相关健康状况治疗策略方面的有前景的作用。
