Department of Pharmacology, University of Kansas, Lawrence, KS, USA.
FASEB J. 2010 Apr;24(4):1261-70. doi: 10.1096/fj.09-147207. Epub 2009 Nov 25.
The enzyme retinol saturase (RetSat) catalyzes the saturation of all-trans-retinol to produce (R)-all-trans-13,14-dihydroretinol. As a peroxisome proliferator-activated receptor (PPAR) gamma target, RetSat was shown to be required for adipocyte differentiation in the 3T3-L1 cell culture model. To understand the mechanism involved in this putative proadipogenic effect of RetSat, we studied the consequences of ablating RetSat expression on retinoid metabolism and adipose tissue differentiation in RetSat-null mice. Here, we report that RetSat-null mice have normal levels of retinol and retinyl palmitate in liver, serum, and adipose tissue, but, in contrast to wild-type mice, are deficient in the production of all-trans-13,14-dihydroretinol from dietary vitamin A. Despite accumulating more fat, RetSat-null mice maintained on either low-fat or high-fat diets gain weight and have similar rates of food intake as age- and gender-matched wild-type control littermates. This increased adiposity of RetSat-null mice is associated with up-regulation of PPARgamma, a key transcriptional regulator of adipogenesis, and also its downstream target, fatty acid-binding protein 4 (FABP4/aP2). On the basis of these results, we propose that dihydroretinoids produced by RetSat control physiological processes that influence PPARgamma activity and regulate lipid accumulation in mice.-Moise, A. R., Lobo, G. P., Erokwu, B., Wilson, D. L., Peck, D., Alvarez, S., Domínguez, M., Alvarez, R., Flask, C. A., de Lera, A. R., von Lintig, J., Palczewski, K. Increased adiposity in the retinol saturase-knockout mouse.
视黄醇饱和酶（RetSat）催化全反式视黄醇的饱和反应，生成（R）-全反式-13,14-二氢视黄醇。作为过氧化物酶体增殖物激活受体（PPAR）γ的靶标，RetSat 在 3T3-L1 细胞培养模型中被证明是脂肪细胞分化所必需的。为了了解 RetSat 在这种假定的促脂肪生成作用中的机制，我们研究了在 RetSat 基因敲除小鼠中消除 RetSat 表达对视黄醇代谢和脂肪组织分化的影响。在这里，我们报告 RetSat 基因敲除小鼠肝脏、血清和脂肪组织中的视黄醇和视黄醇棕榈酸酯水平正常，但与野生型小鼠不同的是，它们缺乏从饮食维生素 A 产生的全反式-13,14-二氢视黄醇。尽管积累了更多的脂肪，但在低脂或高脂饮食下的 RetSat 基因敲除小鼠体重增加，并且与年龄和性别匹配的野生型对照同窝小鼠的食物摄入量相似。RetSat 基因敲除小鼠这种增加的肥胖与 PPARγ的上调有关，PPARγ是脂肪生成的关键转录调节因子，也是其下游靶标脂肪酸结合蛋白 4（FABP4/aP2）。基于这些结果，我们提出 RetSat 产生的二氢视黄醇控制影响 PPARγ 活性并调节小鼠脂质积累的生理过程。
