Uncoupling Lipid Synthesis from Adipocyte Development.

Uncoupling Lipid Synthesis from Adipocyte Development.
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DOI:
10.3390/biomedicines11041132
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发表时间:
2023-04-09
期刊:
影响因子:
4.7
通讯作者:
--
中科院分区:
工程技术3区
文献类型:
--
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肥胖是由脂肪组织的扩张引起的,脂肪组织是一种调节能量平衡、脂肪因子分泌、产热和炎症的多功能组织。脂肪细胞的主要功能被认为是通过脂肪合成储存脂肪,这可能与脂肪生成交织在一起。然而,在长时间的禁食过程中,脂肪细胞耗尽了脂滴,但仍保留了内分泌功能和对营养的即时反应。这一观察让我们质疑,脂肪的合成和储存是否可以从脂肪生成和脂肪细胞功能中分离出来。通过抑制脂肪细胞发育过程中脂肪合成途径中的关键酶,我们证明了基础水平的脂肪合成对于脂肪形成的启动是必不可少的,但对脂肪细胞的成熟和维持特性并不是必需的。此外,诱导成熟脂肪细胞去分化会破坏脂肪细胞的特性,但不会破坏脂肪的储存。这些发现表明,脂肪细胞的脂肪合成和储存不是决定性的特征,并增加了将脂肪细胞发育过程中的脂肪合成解偶联以获得更小和更健康的脂肪细胞用于治疗肥胖和相关疾病的可能性。
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.
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