Lin Tonghui, Mohammad Aftab, Kolonin Mikhail G, Eckel-Mahan Kristin L
The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Molecular and Translational Biology Program, MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.
Immunometabolism (Cobham). 2024 Aug 28;6(3):e00046. doi: 10.1097/IN9.0000000000000046. eCollection 2024 Jul.
In recent decades, obesity has become a worldwide epidemic. As a result, the importance of adipose tissue (AT) as a metabolically active storage depot for lipids and a key mediator of body-wide metabolism and energy balance has been increasingly recognized. Emerging from the studies of AT in metabolic disease is a recognition of the importance of the adipocyte progenitor cell (APC) population of AT being the gatekeeper of adipocyte function. APCs have the capability to self-renew and undergo adipogenesis to propagate new adipocytes capable of lipid storage, which is important for maintaining a healthy fat pad, devoid of dysfunctional lipid droplet hypertrophy, inflammation, and fibrosis, which is linked to metabolic diseases, including type 2 diabetes. Like other dividing cells, APCs are at risk for undergoing cell senescence, a state of irreversible cell proliferation arrest that occurs under a variety of stress conditions, including DNA damage and telomere attrition. APC proliferation is controlled by a variety of factors, including paracrine and endocrine factors, quality and timing of energy intake, and the circadian clock system. Therefore, alteration in any of the underlying signaling pathways resulting in excessive proliferation of APCs can lead to premature APC senescence. Better understanding of APCs senescence mechanisms will lead to new interventions extending metabolic health.
近几十年来，肥胖已成为一种全球性的流行病。因此，脂肪组织（AT）作为脂质的代谢活跃储存库以及全身代谢和能量平衡的关键调节因子的重要性已得到越来越多的认可。从对代谢疾病中脂肪组织的研究中逐渐认识到，脂肪组织中的脂肪细胞祖细胞（APC）群体作为脂肪细胞功能的守门人的重要性。APC具有自我更新和进行脂肪生成的能力，以产生能够储存脂质的新脂肪细胞，这对于维持健康的脂肪垫很重要，该脂肪垫没有与包括2型糖尿病在内的代谢疾病相关的功能失调的脂质滴肥大、炎症和纤维化。与其他分裂细胞一样，APC有经历细胞衰老的风险，细胞衰老是一种在包括DNA损伤和端粒磨损在内的各种应激条件下发生的不可逆细胞增殖停滞状态。APC的增殖受多种因素控制，包括旁分泌和内分泌因素、能量摄入的质量和时间以及生物钟系统。因此，导致APC过度增殖的任何潜在信号通路的改变都可能导致APC过早衰老。更好地理解APC衰老机制将带来延长代谢健康的新干预措施。
