亮氨酸对高脂高胆固醇喂养小鼠瘦素抵抗影响

Effect of leucine on leptin resistance in mice fed with high fat/cholesterol diet

目的探讨亮氨酸对高脂高胆固醇喂养小鼠体脂和瘦素抵抗的影响。方法 60只雄性C57BL/6J小鼠随机分为对照组、高脂高胆固醇组、低、高剂量亮氨酸组(1.5%、3.0%亮氨酸),干预24周;测定小鼠体重、脂肪重量、血清胆固醇和瘦素水平,Western blot法检测小鼠睾周脂肪组织中瘦素受体(Ob-R)、Janus蛋白酪氨酸激酶2(JAK2)、信号转导和转录激活子3(STAT3)及细胞因子信号转导抑制因子3(SOCS3)的蛋白表达。结果高脂高胆固醇喂养明显升高小鼠体重、脂重和血清胆固醇水平;与高脂高胆固醇组比较,亮氨酸组小鼠体重、脂重和血清胆固醇水平明显下降;与对照组比较,高脂高胆固醇组小鼠血清瘦素水平明显升高[(7.14±2.44)ng/mL,](P<0.01);与高脂高胆固醇组比较,1.5%、3.0%亮氨酸组小鼠瘦素水平[分别为(4.21±2.37)、(4.24±2.22)ng/mL]明显降低(P<0.01);与对照组比较,高脂高胆固醇组小鼠睾周脂肪组织中Ob-R蛋白表达下调;与高脂高胆固醇组比较,亮氨酸组小鼠睾周脂肪组织中Ob-R、JAK2蛋白表达上调、SOCS3蛋白表达下调。结论亮氨酸干预可抑制高脂高胆固醇喂养引起的小鼠体重和体脂增加,其机制可能与调节瘦素受体及其下游蛋白JAK2和SOCS3表达、改善瘦素抵抗有关。

Objective To investigate the effect of leucine on fat mass and leptin resistance in mice fed with a high-fat/ cholesterol （HFC） diet. Methods Sixty male C57BL/6J mice were randomly divided into four groups： control group, high fat/cholesterol diet group, low and high leucine （ 1.5% and 3.0% ） groups and treated for 24 weeks. Body weight, fat mass, serum levels of cholesterol and leptin were measured. Protein expression of leptin receptor （ Ob-R）, Janus protein tyrosine kinase 2 （ JAK2 ） , signal transducers and activators of transcription 3 （ STAT3 ）, and suppressors of cytokine signaling 3 （SOCS3） in epididymal adipose tissue were analyzed with Western blot. Results The body weight, fat weight, and serum cholesterol level in the mice of high fat/cholesterol diet group increased, while those in the mice of leucine group decreased significantly. Serum leptin level was significant higher in the mice of high fat/cholesterol diet group than in those of the control group （7. 14±2. 44 vs. 0. 73±0. 42 ng/ml,P 〈0. 01 ）. For the mice of leucine groups,the serum leptin level was deceased （4. 21±2. 37 and 4. 24 ±2. 22 ng/ml） and Ob-R,JAK2 expressions were upregulated, whereas the STAT3 expression was downregulated compared with the mice of high fat/cholestrol diet group. Conclusion Leucine supplementation can suppress weight gain and fat mass in the mice fed with high fat/cholesterol diet probably by regulating the expressions of JAK2 and SOCS3 and improving leptin resistance.