Wan Qianfen, Calhoun Carmen, Zahr Tarik, Qiang Li
Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA.
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Biomedicines. 2023 Apr 9;11(4):1132. doi: 10.3390/biomedicines11041132.
Obesity results from the expansion of adipose tissue, a versatile tissue regulating energy homeostasis, adipokine secretion, thermogenesis, and inflammation. The primary function of adipocytes is thought to be lipid storage through lipid synthesis, which is presumably intertwined with adipogenesis. However, during prolonged fasting, adipocytes are depleted of lipid droplets yet retain endocrine function and an instant response to nutrients. This observation led us to question whether lipid synthesis and storage can be uncoupled from adipogenesis and adipocyte function. By inhibiting key enzymes in the lipid synthesis pathway during adipocyte development, we demonstrated that a basal level of lipid synthesis is essential for adipogenesis initiation but not for maturation and maintenance of adipocyte identity. Furthermore, inducing dedifferentiation of mature adipocytes abrogated adipocyte identity but not lipid storage. These findings suggest that lipid synthesis and storage are not the defining features of adipocytes and raise the possibility of uncoupling lipid synthesis from adipocyte development to achieve smaller and healthier adipocytes for the treatment of obesity and related disorders.
肥胖源于脂肪组织的扩张，脂肪组织是一种多功能组织，可调节能量稳态、脂肪因子分泌、产热和炎症。脂肪细胞的主要功能被认为是通过脂质合成进行脂质储存，这可能与脂肪生成相互交织。然而，在长期禁食期间，脂肪细胞中的脂滴会耗尽，但仍保留内分泌功能并对营养物质产生即时反应。这一观察结果促使我们质疑脂质合成和储存是否可以与脂肪生成及脂肪细胞功能脱钩。通过在脂肪细胞发育过程中抑制脂质合成途径中的关键酶，我们证明了基础水平的脂质合成对于脂肪生成的启动至关重要，但对于脂肪细胞特性的成熟和维持并非如此。此外，诱导成熟脂肪细胞去分化消除了脂肪细胞特性，但并未消除脂质储存。这些发现表明脂质合成和储存并非脂肪细胞的决定性特征，并提出了将脂质合成与脂肪细胞发育脱钩的可能性，以实现更小、更健康的脂肪细胞用于治疗肥胖及相关疾病。
