ApoL6 associates with lipid droplets and disrupts Perilipin1-HSL interaction to inhibit lipolysis.
ApoL6 associates with lipid droplets and disrupts Perilipin1-HSL interaction to inhibit lipolysis.
复制标题
DOI：
10.1038/s41467-023-44559-3
复制
发表时间：
2024-01-02
影响因子：
16.6
通讯作者：
Sul, Hei S.
中科院分区：
文献类型：
--
作者：
Wang, Yuhui;Nguyen, Hai P.;Xue, Pengya;Xie, Ying;Yi, Danielle;Lin, Frances;Dinh, Jennie;Viscarra, Jose A.;Ibe, Nnejiuwa U.;Duncan, Robin E.;Sul, Hei S.
脂肪组织将三酰甘油（TAG）储存在脂滴（LD）中，并在能量不足时通过脂解释放脂肪酸。我们将ApoL 6鉴定为主要在脂肪组织，特别是脂肪细胞中发现的LD相关蛋白。ApoL 6表达在禁食期间较低，但在进食后被诱导。ApoL 6敲低导致脂肪细胞中具有较低TAG含量的较小LD，而ApoL 6过表达导致具有较高TAG含量的较大LD。我们发现ApoL 6通过抑制脂解作用影响脂肪细胞。虽然ApoL 6，Perilipin 1（Plin 1）和HSL可以在LD上形成复合物，但C-末端ApoL 6直接与N-末端Plin 1相互作用，以阻止Plin 1与HSL结合，从而抑制脂解。因此，ApoL 6消融减少了白色脂肪组织质量，保护小鼠免于饮食诱导的肥胖，而ApoL 6在脂肪中的过表达带来肥胖和胰岛素抵抗，使得ApoL 6成为对抗肥胖和糖尿病的潜在未来靶标。脂肪组织中的脂肪分解在禁食期间释放脂肪酸。在这里，作者表明，ApoL 6，一种脂滴相关蛋白，在进食后特异性表达于脂肪细胞中，通过直接与Perilipin 1相互作用以竞争性抑制Perilipin 1-HSL相互作用来抑制脂解。
Adipose tissue stores triacylglycerol (TAG) in lipid droplets (LD) and release fatty acids upon lipolysis during energy shortage. We identify ApoL6 as a LD-associated protein mainly found in adipose tissue, specifically in adipocytes. ApoL6 expression is low during fasting but induced upon feeding. ApoL6 knockdown results in smaller LD with lower TAG content in adipocytes, while ApoL6 overexpression causes larger LD with higher TAG content. We show that the ApoL6 affects adipocytes through inhibition of lipolysis. While ApoL6, Perilipin 1 (Plin1), and HSL can form a complex on LD, C-terminal ApoL6 directly interacts with N-terminal Plin1 to prevent Plin1 binding to HSL, to inhibit lipolysis. Thus, ApoL6 ablation decreases white adipose tissue mass, protecting mice from diet-induced obesity, while ApoL6 overexpression in adipose brings obesity and insulin resistance, making ApoL6 a potential future target against obesity and diabetes. Lipolysis in adipose tissue releases fatty acids during fasting. Here, authors show that ApoL6, a lipid droplet-associated protein, is specifically expressed in adipocytes upon feeding to inhibit lipolysis by directly interacting with Perilipin 1 to competitively inhibit Perilipin 1-HSL interaction.
登录
查看更多内容
影响因子：
5.3
作者：
Kim, Sun-Joong;Tang, Tianyi;Sul, Hei Sook
通讯作者：
Sul, Hei Sook
影响因子：
15.9
作者：
Donnelly, KL;Smith, CI;Parks, EJ
通讯作者：
Parks, EJ
影响因子：
6.5
作者：
Harris, Lydia-Ann L. S.;Shew, Trevor M.;Wolins, Nathan E.
通讯作者：
Wolins, Nathan E.
影响因子：
4.8
作者：
Granneman, James G.;Moore, Hsiao-Ping H.;Rathod, Miloni
通讯作者：
Rathod, Miloni
DOI：
10.1073/pnas.90.24.12035
发表时间：
1993-12-15
影响因子：
11.1
作者：
GREENBERG, AS;EGAN, JJ;KIMMEL, AR
通讯作者：
KIMMEL, AR