摘要
目的:探讨高脂膳食诱导下,不同肥胖程度小鼠血清内源性大麻素(endocannabinoids,EC)、脂肪组织大麻素受体、合成酶和降解酶的变化趋势及其机制。方法:6周龄C57BL/6J雄性小鼠随机分为对照组(n=25,喂食普通饲料)和高脂诱导组(n=205,喂食D12492高脂饲料,脂肪提供热量占60%),诱导时间10周。对照组随机挑选10只平均体重记为X(g);高脂诱导组按体重分类标准分4组(每组随机挑选10只):抵抗组(X×0.9<体重≤X×1.1)、超重组(X×1.1<体重≤X×1.2)、肥胖组(X×1.2<体重≤X×1.5)和严重肥胖组(体重>X×1.5)。采用高效液相色谱法检测血清大麻素含量,荧光定量PCR检测脂肪组织大麻素受体、合成酶和降解酶表达变化。结果:1)从对照组、超重组、肥胖组到严重肥胖组,血清大麻素平均水平依次升高,但只有严重肥胖组血清2-AG、AEA和OEA与对照组相比显著升高(P<0.01,P<0.05和P<0.05)。2)(超重+肥胖+严重肥胖组)VS对照组,脂肪组织大麻素受体CB1,CB2 m NRA表达下降(P<0.05和P<0.05),2-AG合成酶DAGLβ表达上升(P<0.01)。3)将超重、肥胖和严重肥胖组小鼠综合起来分析发现,血清2-AG与体重(P=0.004,r=0.586)和内脏脂肪量(P=0.001,r=0.647)均呈中度正相关,而血清AEA仅与内脏脂肪量呈正相关(P=0.034,r=0.453)。4)内脏脂肪量与脂肪组织2-AG合成酶ABHD4(P=0.022,r=-0.466)、DAGLβ(P=0.019,r=-0.475)、降解酶ABHD6(P=0.000,r=-0.738)、MAGL(P=0.012,r=-0.505)、AEA和OEA的共同降解酶NAAA(P=0.003,r=-0.586)m RNA表达呈负相关。结论:高脂诱导下,超重、肥胖和严重肥胖组小鼠血清循环大麻素水平依次升高,脂肪组织大麻素受体CB1表达依次下降,大麻素合成酶与降解酶与内脏脂肪量均呈负相关。因此我们推测:对于相同诱导时间下的不同肥胖程度小鼠,大麻素合成酶表达下调的速度低于降解酶和CB1受体的下调速度,使得循环大麻素水平升高,这些因素共同促成了肥胖相关的外周ECS�
Objective： To explore the changes of endocannabinoids, related receptor, synthetic enzyme and degrading enzyme in mice of different obese status via high fat diet. Methods： C57BL/6J male mice were randomly divided into control group （n=25, fed normal diet） and high fat diet group （n=205, fed D12492, 60% fat）. For further experiments, 10 mice were randomly selected from control group and recorded average body weight （BW） as X （g） ; for mice fed on high fat diet, four groups were divided., resistant group （X X 0.9 〈 BW≤ X × 1.1 ） ;overweight group （X × 1.1 〈 BW ≤ X× 1.2 ）; obese group （X × 1.2 〈 BW≤ X× 1.5 ） ; severe obese group （BW 〉 X × 1.5 ）. High performance liquid chromatography （HPLC） and RT-PCR were used to detect endocannabinoids levels and expression of related endogenous cannabinoid receptors, synthetic enzyme and degrading enzyme, respectively. Results： 1 ） from control group to severe obese group, serum endocannabinoids increased successively, however, only 2-AG, AEA and OEA in severe group were significantly higher than control group （P〈 0.01, P〈 0.05 and P〈 0.05 ）. 2 ） for overweight, obese and severe group mice, adipose CB1, CB2 mRNA level were lower than control group （P〈 0.05 and P〈 0.05 ）, while 2-AG synthetic enzyme DAGLβ mRNA level were higher than control group （P〈 0.01 ）. For overweight, obese and severe group mice, 3 ） serum2-AG showed moderate positive correlation with BW （P=0.004, r=0.586） and visceral adipose mass （P=0.001, r=0.647） ; while serum AEA were positively correlated with visceral adipose mass （P=0.034, r=0.453 ） only. 4） visceral adipose mass were negatively correlated with synthetic enzyme ABHD4 （P=0.022, r=- 0.466 ）, DAGLβ （P=0.019, r=- 0.475 ）, degrading enzyme ABHD6 （P=0.000, r=-- 0.738）, MAGL （P=0.012, r=- 0.505 ） and NAAA （P=0.003, r=-0.586） mRNA level. Conclusion： serum endocannabinoids increased successively as body weight increased during hig
出处
《中国体育科技》
CSSCI
北大核心
2017年第5期117-124,共8页
China Sport Science and Technology
基金
国家自然科学基金面上资助项目(81472148)
