Cheng Yu, Zhang Kaili, Liu Jisong, Liu Guangpeng
Department of Plastic and Reconstructive Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
Department of Burn and Plastic Surgery, The Third People's Hospital of Bengbu, Bengbu, Anhui, People's Republic of China.
Diabetes Metab Syndr Obes. 2025 Aug 20;18:2977-2984. doi: 10.2147/DMSO.S521845. eCollection 2025.
Obesity is a global health problem characterized by excessive white adipose tissue (WAT) distribution. Adipocyte hypertrophy (increased cell size) and hyperplasia (differentiation into new adipocytes from pre-adipocytes) are two ways for WAT to expand. The precedence of hypertrophy over hyperplasia leads to an enlarged adipocyte size, which is associated with multiple metabolic dysfunctions. Compared with abdominal subcutaneous fat (SF), orbital fat (OF) has smaller adipocytes with less inflammatory infiltration, better vascularization, and higher adipogenic and proliferative capacities, reflecting a healthy metabolic state. Polyunsaturated fatty acids (PUFAs) can stabilize energy homeostasis via G protein-coupled receptor 120 (GPR120) to alleviate insulin resistance and inflammation.
We used lipidomics analysis to reveal a greater accumulation of two PUFAs-arachidonic acid (AA) and docosapentaenoic acid (DPA) in OF than in SF and then hypothesized that AA/DPA is one factor regulating WAT morphological and biological heterogeneity.
Mechanistically, the existing literature evidence suggests that AA/DPA signals may stimulate the co-activation and interaction of GPR120 and peroxisome proliferator-activated receptor γ (PPARγ), at least partially contributing to adipose metabolic health.
As the differential metabolites between OF and SF, AA and DPA, along with the relevant GPR120/PPARγ pathways, offer new therapeutic approaches for morbid obesity.
肥胖是一个全球性的健康问题,其特征是白色脂肪组织(WAT)分布过多。脂肪细胞肥大(细胞大小增加)和增生(前脂肪细胞分化为新的脂肪细胞)是WAT扩张的两种方式。肥大先于增生会导致脂肪细胞大小增大,这与多种代谢功能障碍有关。与腹部皮下脂肪(SF)相比,眼眶脂肪(OF)的脂肪细胞较小,炎症浸润较少,血管化程度更高,脂肪生成和增殖能力更强,反映出一种健康的代谢状态。多不饱和脂肪酸(PUFA)可通过G蛋白偶联受体120(GPR120)稳定能量稳态,以减轻胰岛素抵抗和炎症。
我们使用脂质组学分析揭示了OF中两种PUFA——花生四烯酸(AA)和二十二碳五烯酸(DPA)的积累比SF中更多,然后推测AA/DPA是调节WAT形态和生物学异质性的一个因素。
从机制上讲,现有文献证据表明,AA/DPA信号可能刺激GPR120和过氧化物酶体增殖物激活受体γ(PPARγ)的共激活和相互作用,至少部分有助于脂肪代谢健康。
作为OF和SF之间的差异代谢物,AA和DPA以及相关的GPR120/PPARγ途径为病态肥胖提供了新的治疗方法。