Division of Endocrinology, Dalhousie University, 1278 Tower Road, Halifax, NS, Canada.
Diab Vasc Dis Res. 2010 Jul;7(3):231-8. doi: 10.1177/1479164110369848. Epub 2010 May 14.
The RAS is a novel target in the study of diabetes, and clinical trials have indicated that ARBs, such as valsartan, may exert some of their clinical effects through an influence on adipose tissue. We studied the effect of valsartan on adipokine genes resistin (rstn) and fasting-induced adipose factor (fiaf) using obese and diabetic ob/ob mice. In addition to visceral and subcutaneous fat, rstn and fiaf mRNA levels were also measured in several other tissues known to express these adipokines, including the pituitary, cerebral cortex and hypothalamus. The significant findings were that (a) fiaf gene expression was elevated two- to fourfold in visceral and subcutaneous fat from ob/ob mice, compared with lean controls; (b) the increase in fiaf mRNA in subcutaneous, but not visceral, fat from ob/ob mice was returned to lean control levels following 2 weeks of valsartan treatment; (c) fiaf expression was reduced in the hypothalamus, but not in the cortex or pituitary, of ob/ob mice; (d) rstn expression was greatly reduced in visceral fat from ob/ob mice, compared with lean controls, but this was unaffected by valsartan; and (e) rstn expression was unchanged in all other tissues from ob/ob mice, with or without valsartan treatment.
RAS 是糖尿病研究中的一个新靶点，临床试验表明血管紧张素受体拮抗剂（如缬沙坦）可能通过对脂肪组织的影响发挥其部分临床作用。我们研究了缬沙坦对肥胖和糖尿病 ob/ob 小鼠脂肪因子抵抗素（rstn）和禁食诱导脂肪因子（fiaf）基因的影响。除了内脏和皮下脂肪外，还在已知表达这些脂肪因子的其他几种组织中测量了 rstn 和 fiaf mRNA 水平，包括垂体、大脑皮层和下丘脑。主要发现是：（a）与瘦对照组相比，ob/ob 小鼠内脏和皮下脂肪中的 fiaf 基因表达升高了两到四倍；（b）ob/ob 小鼠皮下脂肪而不是内脏脂肪中的 fiaf mRNA 增加在 2 周缬沙坦治疗后恢复到瘦对照组水平；（c）ob/ob 小鼠下丘脑的 fiaf 表达减少，但皮质或垂体没有减少；（d）与瘦对照组相比，ob/ob 小鼠的内脏脂肪中 rstn 表达大大降低，但缬沙坦对其没有影响；（e）ob/ob 小鼠的所有其他组织中的 rstn 表达均无变化，无论是否使用缬沙坦。
