Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Diabetes. 2012 May;61(5):1112-21. doi: 10.2337/db11-1620. Epub 2012 Mar 6.
Retinoic acid (RA) protects mice from diet-induced obesity. The activity is mediated in part through activation of the nuclear receptors RA receptors (RARs) and peroxisome proliferator-activated receptor β/δ and their associated binding proteins cellular RA binding protein type II (CRABP-II) and fatty acid binding protein type 5 in adipocytes and skeletal muscle, leading to enhanced lipid oxidation and energy dissipation. It was also reported that RA inhibits differentiation of cultured preadipocytes. However, whether the hormone suppresses adipogenesis in vivo and how the activity is propagated remained unknown. In this study, we show that RA inhibits adipocyte differentiation by activating the CRABP-II/RARγ path in preadipose cells, thereby upregulating the expression of the adipogenesis inhibitors Pref-1, Sox9, and Kruppel-like factor 2 (KLF2). In turn, KLF2 induces the expression of CRABP-II and RARγ, further potentiating inhibition of adipocyte differentiation by RA. The data also indicate that RA suppresses adipogenesis in vivo and that the activity significantly contributes to the ability of the hormone to counteract diet-induced obesity.
视黄酸（RA）可保护小鼠免受饮食诱导的肥胖。这种作用部分是通过激活核受体 RA 受体（RARs）和过氧化物酶体增殖物激活受体β/δ及其在脂肪细胞和骨骼肌中的相关结合蛋白细胞 RA 结合蛋白 II（CRABP-II）和脂肪酸结合蛋白 5 来介导的，导致脂质氧化和能量消耗增强。据报道，RA 还抑制培养的前体脂肪细胞的分化。然而，该激素是否在体内抑制脂肪生成以及该活性如何传播尚不清楚。在这项研究中，我们表明 RA 通过激活前脂肪细胞中的 CRABP-II/RARγ 途径来抑制脂肪细胞分化，从而上调脂肪生成抑制剂 Pref-1、Sox9 和 Kruppel 样因子 2（KLF2）的表达。反过来，KLF2 诱导 CRABP-II 和 RARγ 的表达，进一步增强 RA 对脂肪细胞分化的抑制作用。数据还表明，RA 在体内抑制脂肪生成，并且该活性显著有助于激素对抗饮食诱导的肥胖的能力。
