Caveolin-1 deficiency leads to increased susceptibility to cell death and fibrosis in white adipose tissue: characterization of a lipodystrophic model.
Caveolin-1 deficiency leads to increased susceptibility to cell death and fibrosis in white adipose tissue: characterization of a lipodystrophic model.
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DOI：
10.1371/journal.pone.0046242
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Parton RG
中科院分区：
文献类型：
--
作者：
Martin S;Fernandez-Rojo MA;Stanley AC;Bastiani M;Okano S;Nixon SJ;Thomas G;Stow JL;Parton RG
小窝蛋白-1 （CAV1）是脂肪组织稳态的重要调节因子。在本研究中，我们研究了在代谢应激条件下CAV1缺乏对小鼠体内和外植体培养脂肪组织特性的影响。在CAV1−/−小鼠中，尽管缺乏激素敏感脂肪酶（HSL）磷酸化，但禁食引起脂肪组织质量的损失。此外，禁食导致巨噬细胞浸润增加，胶原沉积增强，脂滴蛋白periilipin a （PLIN1a）水平降低。CAV1−/−脂肪组织的外植体培养也显示PLIN1a在培养过程中丢失，IL-6分泌增强，乳酸脱氢酶释放增加，并且在胶原酶处理下对细胞死亡的易感性增加。在CAV1+/+饮食性肥胖小鼠的脂肪组织外植体中，还观察到pka介导的HSL信号减弱、PLIN1a缺失和IL-6分泌增加。综上所述，这些结果表明，在CAV1 - / -小鼠中，虽然脂肪细胞脂滴生物学的改变在缺乏pka介导的促脂解信号的情况下支持脂肪组织代谢，但组织本质上是不稳定的，导致细胞死亡的易感性增加，我们认为这是代谢应激期间纤维化和炎症发展的基础。
Caveolin-1 (CAV1) is an important regulator of adipose tissue homeostasis. In the present study we examined the impact of CAV1 deficiency on the properties of mouse adipose tissue both in vivo and in explant cultures during conditions of metabolic stress. In CAV1−/− mice fasting caused loss of adipose tissue mass despite a lack of hormone-sensitive lipase (HSL) phosphorylation. In addition, fasting resulted in increased macrophage infiltration, enhanced deposition of collagen, and a reduction in the level of the lipid droplet protein perilipin A (PLIN1a). Explant cultures of CAV1−/− adipose tissue also showed a loss of PLIN1a during culture, enhanced secretion of IL-6, increased release of lactate dehydrogenase, and demonstrated increased susceptibility to cell death upon collagenase treatment. Attenuated PKA-mediated signaling to HSL, loss of PLIN1a and increased secretion of IL-6 were also observed in adipose tissue explants of CAV1+/+ mice with diet-induced obesity. Together these results suggest that while alterations in adipocyte lipid droplet biology support adipose tissue metabolism in the absence of PKA-mediated pro-lipolytic signaling in CAV1−/− mice, the tissue is intrinsically unstable resulting in increased susceptibility to cell death, which we suggest underlies the development of fibrosis and inflammation during periods of metabolic stress.
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影响因子：
6.5
作者：
Kimmel AR;Brasaemle DL;McAndrews-Hill M;Sztalryd C;Londos C
通讯作者：
Londos C
DOI：
10.1083/jcb.200903053
发表时间：
2009-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bastiani M;Liu L;Hill MM;Jedrychowski MP;Nixon SJ;Lo HP;Abankwa D;Luetterforst R;Fernandez-Rojo M;Breen MR;Gygi SP;Vinten J;Walser PJ;North KN;Hancock JF;Pilch PF;Parton RG
通讯作者：
Parton RG
影响因子：
4.8
作者：
Liu, Libin;Pilch, Paul F.
通讯作者：
Pilch, Paul F.
影响因子：
5.8
作者：
Kim, C. A.;Delepine, Marc;Magre, Jocelyne
通讯作者：
Magre, Jocelyne
影响因子：
56.9
作者：
Drab, M;Verkade, P;Kurzchalia, TV
通讯作者：
Kurzchalia, TV