Department of Medicine, The University of Hong Kong, Hong Kong, China.
PLoS One. 2013 Jun 12;8(6):e65543. doi: 10.1371/journal.pone.0065543. Print 2013.
This study was designed to (1) investigate the expression profiles of resistin in db/db mice and its dynamic association with metabolic parameters; and (2) evaluate the effects of Rosiglitazone on production of resistin.
Db/db mice and their lean litter mates were used for this study. Epididymal fat tissue was excised from mice of different age (from 5 to 12 weeks) for ex vivo incubation. Resistin,along with adiponectin,in serum and conditioned culture medium of epididymal fat pads were measured with immunoassays. The gene expression of resistin was determined by real-time PCR. Rosiglitazone or the vehicle (PBS) was administered into db/db mice by daily intra-gastric gavage. Differentiated 3T3-L1 adipocytes were used for in vitro evaluation.
The secretion of resistin from the fat pads in db/db mice was significantly lower than that in lean mice (P<0.01). The mRNA expression of the resistin gene in fat tissue of db/db mice at the age of 5 weeks was decreased by 60.5% compared to lean controls (p<0.05). Serum levels of resistin were comparable between the obese and lean groups, perhaps due to the increased total fat mass in db/db mice. Correlation analysis showed that serum resistin levels were positively correlated to resistin secretion from fat pads(r = 0.844,P = 0.000), while negatively associated with the body weight (r = -0.515, P = 0.000) and fasting glucose level (r = -0.357, P = 0.002). Notably, treatment with rosiglitazone increased the serum resistin levels by 66.4%(P<0.05)in db/db mice. In 3T3-L1 adipocytes, Rosiglitazone (10 uM) markedly enhanced the secretion of resistin by 120% (P<0.01) and its gene expression by 78.1% (P<0.05).
Both resistin gene expression and its secretion from the epididymal adipose tissue were decreased in db/db obese mice, while the insulin-sensitizing drug rosiglitazone increased resistin production. Our results do not support the role of resistin as an etiological link between obesity and diabetes.
本研究旨在：(1) 研究抵抗素在 db/db 小鼠中的表达谱及其与代谢参数的动态关联；(2) 评估罗格列酮对抵抗素产生的影响。
本研究使用 db/db 小鼠及其瘦型同窝小鼠。从不同年龄(5-12 周)的小鼠中切除附睾脂肪组织进行离体孵育。用免疫分析法测定血清和附睾脂肪垫条件培养基中的抵抗素和脂联素。实时 PCR 测定抵抗素基因的表达。通过每日胃内灌胃给予 db/db 小鼠罗格列酮或载体(PBS)。分化的 3T3-L1 脂肪细胞用于体外评价。
db/db 小鼠脂肪垫中抵抗素的分泌明显低于瘦型小鼠(P<0.01)。5 周龄 db/db 小鼠脂肪组织中抵抗素基因的 mRNA 表达与瘦型对照组相比降低了 60.5%(p<0.05)。肥胖组和瘦型组血清抵抗素水平相当，可能是由于 db/db 小鼠总脂肪量增加。相关性分析显示，血清抵抗素水平与脂肪垫中抵抗素分泌呈正相关(r=0.844，P=0.000)，与体重(r=-0.515，P=0.000)和空腹血糖水平(r=-0.357，P=0.002)呈负相关。值得注意的是，罗格列酮治疗使 db/db 小鼠血清抵抗素水平升高 66.4%(P<0.05)。在 3T3-L1 脂肪细胞中，罗格列酮(10 μM)显著增加抵抗素分泌 120%(P<0.01)和基因表达 78.1%(P<0.05)。
db/db 肥胖小鼠附睾脂肪组织中抵抗素基因表达及其分泌均降低，而胰岛素增敏药罗格列酮增加抵抗素产生。我们的结果不支持抵抗素作为肥胖与糖尿病之间病因联系的作用。
