Adipose Factor ANGPTL4: Its Role in Aging Mechanisms and Associated Diseases.

IF 3.5 3区 医学 Q2 GERIATRICS & GERONTOLOGY
Clinical Interventions in Aging Pub Date : 2025-06-28 eCollection Date: 2025-01-01 DOI:10.2147/CIA.S522049
Xiaojun Wang, Hung-Chen Chang, Xuchao Gu, Yuxin Zhang, Zhijun Bao
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引用次数: 0

Abstract

The angiopoietin-like protein 4 (ANGPTL4), also known as fasting-induced adipose factor, is a secreted glycoprotein that belongs to the ANGPTL protein family. Due to its expression in various cell types and tissues and its interactions with other proteins, ANGPTL4 plays diverse roles within its family, exhibiting a wider range of molecular functions. For instance, ANGPTL4 is intricately involved in modulating central energy metabolism and enhancing exercise endurance, while also acting as a pivotal mediator in the interaction between gut microbiota and host lipid metabolism. Moreover, the expression of ANGPTL4 is directly controlled by aging-related signaling pathways. Its excessive activation accelerates the aging process by triggering mechanisms like heightened oxidative stress, epithelial-mesenchymal transition (EMT) and fibrosis, abnormal lipid accumulation, and cellular arrest, thereby advancing the development of age-related diseases. Given the pivotal roles of ANGPTL4 and its associated molecules in organ fibrosis and cancer advancement, targeting ANGPTL4 emerges as a promising therapeutic approach. However, the intricate and sometimes conflicting functions of the two cleavage fragments of ANGPTL4, namely N-terminal fragment (nANGPTL4) and C-terminal fragment (cANGPTL4), in different chronic diseases-exerting inhibitory or stimulatory effects depending on the disease stage-have posed challenges to the progress of ANGPTL4 antibody therapy. This review provides an overview of the biological mechanisms of ANGPTL4, its dual impact on fibrosis and tumorigenesis, and highlights its recent advancements as a potential biomarker in age-related diseases and inflammation-related conditions. ANGPTL4 is a high-potential but complex target, requiring mechanism-driven strategies for safe clinical translation.

脂肪因子ANGPTL4在衰老机制和相关疾病中的作用
血管生成素样蛋白4 (ANGPTL4),又称空腹诱导脂肪因子,是一种分泌型糖蛋白,属于angptl1蛋白家族。由于ANGPTL4在多种细胞类型和组织中表达,并与其他蛋白相互作用,因此在其家族中发挥着多种作用,表现出更广泛的分子功能。例如,ANGPTL4复杂地参与调节中枢能量代谢和增强运动耐力,同时也是肠道微生物群与宿主脂质代谢相互作用的关键介质。此外,ANGPTL4的表达受衰老相关信号通路的直接控制。它的过度激活通过触发氧化应激升高、上皮-间质转化(EMT)和纤维化、异常脂质积累和细胞停滞等机制加速衰老过程,从而促进年龄相关疾病的发展。鉴于ANGPTL4及其相关分子在器官纤维化和癌症进展中的关键作用,靶向ANGPTL4成为一种很有前景的治疗方法。然而,ANGPTL4的两个切割片段,即n端片段(nANGPTL4)和c端片段(cANGPTL4)在不同慢性疾病中的复杂且有时相互冲突的功能-根据疾病阶段发挥抑制或刺激作用-给ANGPTL4抗体治疗的进展带来了挑战。本文综述了ANGPTL4的生物学机制、其在纤维化和肿瘤发生中的双重作用,并重点介绍了其作为年龄相关疾病和炎症相关疾病的潜在生物标志物的最新进展。ANGPTL4是一个高潜力但复杂的靶点,需要机制驱动的策略来实现安全的临床转化。
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来源期刊
Clinical Interventions in Aging
Clinical Interventions in Aging GERIATRICS & GERONTOLOGY-
CiteScore
6.80
自引率
2.80%
发文量
193
审稿时长
6-12 weeks
期刊介绍: Clinical Interventions in Aging, is an online, peer reviewed, open access journal focusing on concise rapid reporting of original research and reviews in aging. Special attention will be given to papers reporting on actual or potential clinical applications leading to improved prevention or treatment of disease or a greater understanding of pathological processes that result from maladaptive changes in the body associated with aging. This journal is directed at a wide array of scientists, engineers, pharmacists, pharmacologists and clinical specialists wishing to maintain an up to date knowledge of this exciting and emerging field.
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