Intact vitamin A transport is critical for cold-mediated adipose tissue browning and thermogenesis.
Intact vitamin A transport is critical for cold-mediated adipose tissue browning and thermogenesis.
复制标题
DOI：
10.1016/j.molmet.2020.101088
复制
发表时间：
2020-12
影响因子：
8.1
通讯作者：
Kiefer FW
中科院分区：
文献类型：
--
作者：
Fenzl A;Kulterer OC;Spirk K;Mitulović G;Marculescu R;Bilban M;Baumgartner-Parzer S;Kautzky-Willer A;Kenner L;Plutzky J;Quadro L;Kiefer FW
在许多临床前模型中，白色脂肪转化为棕色脂肪（“褐变”）可以减少肥胖，并且作为代谢性疾病的治疗概念具有很大的前景。维生素A代谢物（类维生素A）与脂肪组织的产热程序有关；然而，系统性类维生素a转运对脂肪组织褐变和适应性产热的生理重要性尚不清楚。我们在小鼠和人类中进行了冷暴露研究，并使用维生素a运输缺陷的遗传模型，视黄醇结合蛋白缺陷（Rbp - /-）小鼠，研究冷却对全身维生素a的影响以及完整的类视黄醇运输与冷诱导的脂肪组织褐变的相关性。我们发现，小鼠和人类的冷刺激导致循环视黄醇及其血浆转运体Rbp的增加。在Rbp - /-小鼠中，皮下白色脂肪中脂肪细胞的产热编程和线粒体氧化功能显著受损，这使得Rbp - /-小鼠对冷敏感。相反，视黄醇刺激原代人脂肪细胞可促进产热基因表达和线粒体呼吸。在人类中，冷介导的视黄醇增加与氧化底物代谢的改变有关，这表明脂质利用率较高。小鼠和人类的全身维生素A水平受寒冷暴露的调节，完整的类维生素A转运对于冷诱导的脂肪组织褐变和适应性产热至关重要。
Transformation of white into brown fat (“browning”) reduces obesity in many preclinical models and holds great promise as a therapeutic concept in metabolic disease. Vitamin A metabolites (retinoids) have been linked to thermogenic programming of adipose tissue; however, the physiologic importance of systemic retinoid transport for adipose tissue browning and adaptive thermogenesis is unknown. We performed cold exposure studies in mice and humans and used a genetic model of defective vitamin A transport, the retinol binding protein deficient (Rbp−/-) mouse, to study the effects of cooling on systemic vitamin A and the relevance of intact retinoid transport on cold-induced adipose tissue browning. We show that cold stimulation in mice and humans leads to an increase in circulating retinol and its plasma transporter, Rbp. In Rbp−/- mice, thermogenic programming of adipocytes and oxidative mitochondrial function are dramatically impaired in subcutaneous white fat, which renders Rbp−/- mice more cold-sensitive. In contrast, retinol stimulation in primary human adipocytes promotes thermogenic gene expression and mitochondrial respiration. In humans, cold-mediated retinol increase is associated with a shift in oxidative substrate metabolism suggestive of higher lipid utilisation. Systemic vitamin A levels are regulated by cold exposure in mice and humans, and intact retinoid transport is essential for cold-induced adipose tissue browning and adaptive thermogenesis.
登录
查看更多内容
影响因子：
56.9
作者：
BLOMHOFF, R;GREEN, MH;NORUM, KR
通讯作者：
NORUM, KR
视网膜甲醛脱氢酶1调节白色脂肪组织中的热程序。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.1
作者：
Alvarez, R;Checa, M;Villarroya, F
通讯作者：
Villarroya, F
影响因子：
4.8
作者：
Kiefer, Florian W.;Orasanu, Gabriela;Plutzky, Jorge
通讯作者：
Plutzky, Jorge
影响因子：
4.8
作者：
Clugston, Robin D.;Huang, Li-Shin;Blaner, William S.
通讯作者：
Blaner, William S.