Sexual Medicine and Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, 6, Florence 50139, Italy.
J Endocrinol. 2012 Dec;215(3):347-62. doi: 10.1530/JOE-12-0333. Epub 2012 Oct 8.
We recently demonstrated that testosterone dosing ameliorated the metabolic profile and reduced visceral adipose tissue (VAT) in a high-fat diet (HFD)-induced rabbit model of metabolic syndrome (MetS). We studied the effects of HFD and in vivo testosterone dosing on VAT function and the adipogenic capacity of rabbit preadipocytes isolated from VAT of regular diet (RD), HFD, and testosterone-treated HFD rabbits. VAT was studied by immunohistochemistry, western blot, and RT-PCR. Isolated rPADs were exposed to adipocyte differentiating mixture (DIM) to evaluate adipogenic potential. Adipocyte size was significantly increased in HFD VAT compared with RD, indicating adipocyte dysfunction, which was normalized by testosterone dosing. Accordingly, perilipin, an anti-lipolytic protein, was significantly increased in HFD VAT, when compared with other groups. HFD VAT was hypoxic, while testosterone dosing normalized VAT oxygenation. In VAT, androgen receptor expression was positively associated with mRNA expression of GLUT4 (SLC2A4) (insulin-regulated glucose transporter) and STAMP2 (STEAP4) (androgen-dependent gene required for insulin signaling). In testosterone-treated HFD VAT, STAMP2 mRNA was significantly increased when compared with the other groups. Moreover, GLUT4 membrane translocation was significantly reduced in HFD VAT, compared with RD, and increased by testosterone. In DIM-exposed preadipocytes from HFD, triglyceride accumulation, adipocyte-specific genes, insulin-stimulated triglyceride synthesis, glucose uptake, and GLUT4 membrane translocation were reduced compared with preadipocytes from RD and normalized by in vivo testosterone dosing. In conclusion, testosterone dosing in a MetS animal model positively affects VAT functions. This could reflect the ability of testosterone in restoring insulin sensitivity in VAT, thus counteracting metabolic alterations.
我们最近证明，睾酮给药可改善高脂肪饮食（HFD）诱导的代谢综合征（MetS）兔模型的代谢特征并减少内脏脂肪组织（VAT）。我们研究了 HFD 和体内睾酮给药对 VAT 功能以及从正常饮食（RD）、HFD 和睾酮治疗的 HFD 兔的 VAT 分离的兔前体脂肪细胞（rPAD）的脂肪生成能力的影响。通过免疫组织化学，Western blot 和 RT-PCR 研究 VAT。将分离的 rPAD 暴露于脂肪细胞分化混合物（DIM）中以评估脂肪生成潜力。与 RD 相比，HFD 的 VAT 中脂肪细胞明显增大，表明脂肪细胞功能障碍，这通过睾酮给药得到了纠正。相应地，抗脂解蛋白 perilipin 在 HFD 的 VAT 中与其他组相比显着增加。HFD 的 VAT 呈缺氧状态，而睾酮给药可使 VAT 氧合正常化。在 VAT 中，雄激素受体表达与葡萄糖转运蛋白 4（SLC2A4）（胰岛素调节的葡萄糖转运蛋白）和 STAMP2（STEAP4）（胰岛素信号必需的雄激素依赖性基因）的 mRNA 表达呈正相关。在 HFD 的睾酮治疗的 VAT 中，与其他组相比，STAMP2 mRNA 显着增加。此外，与 RD 相比，HFD 的 VAT 中 GLUT4 膜转位显着减少，而睾酮增加了 GLUT4 膜转位。在 HFD 的 DIM 暴露的前体脂肪细胞中，与 RD 的前体脂肪细胞相比，甘油三酸酯积累，脂肪细胞特异性基因，胰岛素刺激的甘油三酯合成，葡萄糖摄取和 GLUT4 膜转位减少，并通过体内睾酮给药得到纠正。总之，在 MetS 动物模型中给予睾酮可对 VAT 功能产生积极影响。这可能反映了睾酮恢复 VAT 胰岛素敏感性的能力，从而抵消了代谢改变。
