PDF(Pubmed)
Abstract：
Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the circulation exclusively from hepatocytes, thereby mobilizing hepatic retinoid stores that represent the major vitamin A reserves in the body. The relevance of extrahepatic retinoid stores for circulating retinol and RBP4 levels that are usually kept within narrow physiological limits is unknown. Here, we show that fasting affects retinoid mobilization in a tissue-specific manner, and that hormone-sensitive lipase (HSL) in adipose tissue is required to maintain serum concentrations of retinol and RBP4 during fasting in mice. We found that extracellular retinol-free apo-RBP4 induces retinol release by adipocytes in an HSL-dependent manner. Consistently, global or adipocyte-specific HSL deficiency leads to an accumulation of retinoids in adipose tissue and a drop of serum retinol and RBP4 during fasting, which affects retinoid-responsive gene expression in eye and kidney and lowers renal retinoid content. These findings establish a novel crosstalk between liver and adipose tissue retinoid stores for the maintenance of systemic vitamin A homeostasis during fasting.
摘要：
维生素A（视黄醇）通过结合其特定载体蛋白的血液分布，视黄醇结合蛋白4(RBP4)。视黄醇负载的RBP4是分泌到循环专门从肝细胞，从而动员代表体内主要维生素A储备的肝脏类维生素A储备。肝外类维生素A储存与循环视黄醇和RBP4水平的相关性通常保持在狭窄的生理范围内是未知的。这里,我们显示禁食以组织特异性方式影响类维生素A动员，并且在小鼠禁食期间维持血清视黄醇和RBP4浓度需要脂肪组织中的激素敏感脂肪酶（HSL）。我们发现，无细胞外视黄醇的apo-RBP4以HSL依赖性方式诱导脂肪细胞释放视黄醇。始终如一，全局性或脂肪细胞特异性HSL缺乏导致脂肪组织中类维生素A的积累，以及空腹时血清视黄醇和RBP4的下降，这会影响眼和肾脏中的类维生素A反应基因表达并降低肾脏类维生素A含量。这些发现建立了肝脏和脂肪组织类维生素A储存之间的新型串扰，以维持禁食期间的全身维生素A稳态。
