哺乳期营养过剩对幼年小鼠肝细胞脂质代谢及超微结构的影响

目的探讨哺乳期营养过剩与肝脏线粒体改变及脂质代谢的关系。方法 ICR品系孕鼠分娩后D5,通过调整每窝子鼠数量,建立出生后哺乳期营养过剩动物模型。每只母鼠哺乳10只子鼠设为对照组(CTR),调整后每只母鼠哺乳3只子鼠设为哺乳期营养过剩组(LON)。21 d处死子鼠取肝脏,采用透射电镜技术观察肝细胞线粒体改变,HE染色观察肝组织形态学改变,实时荧光定量PCR检测动物肝脏组织肉碱酯酰转移酶-1(CPT-1)、硬脂酰辅酶A去饱和酶-1(SCD-1)及脂肪酸合成酶(FASN)mRNA表达水平,Western blot检测肝脏中CPT-1和细胞色素C(Cyt-C)的蛋白表达。结果哺乳期营养过剩可以导致子代肥胖(P<0.001),肝脏组织脂质沉积明显,SCD-1和FASN基因表达水平升高(P<0.01),肝细胞出现线粒体肿胀,并伴有CTP-1基因和蛋白水平表达降低(P<0.01),细胞色素C表达降低(P<0.01)。结论哺乳期营养过剩能促进肝脏脂质沉积,该作用可能与肝细胞线粒体功能改变、脂肪酸β-氧化水平降低及脂质合成增多有关。哺乳期营养过剩可能是诱发成年期脂肪肝的重要危险因素。[营养学报,2012,34(6):540-544]

EFFECTS OF OVER-NUTRITION IN LACTATING PERIOD ON HEPATIC LIPID METABOLISM AND HEPATOCYTE ULTRA-STRUCTURE IN INFANT MICE

Objective To examine the effects of over-nutrition in lactating period on hepatic lipid metabolism and ultra-structure change in hepatocytes.Method The offsprings of ICR mice were divided into two groups after delivery.In lactating over-nutrition(LON) group,the litters were adjusted to 3 pups per dam,while 10 pups in each dam in control group(CTR).The body weight of the pups was measured and all animals were sacrificed and the livers were obtained for histological analysis by H&E staining at the age of 3 w.The ultra-structure changes of hepatocyte were observed under transmission electron microscope.The mRNA levels of carnitine acyl transferase-1(CPT-1),stearoyl-CoA desaturase-1(SCD-1) and fatty acid synthase(FASN)in liver tissues were detected by real-time quantitative PCR.CPT-1 and cytochrome C(Cyt-C) proteins were determined by Western blot.Results Over-nutrition in lactating period induced a rapid weight gain(P<0.001) and lipid deposition in the liver,associated with up-regulation of genes of SCD-1 and FASN(P<0.01).An apparent mitochondrial swelling in hepatocytes was observed in LON mice,accompanied with down-regulation of CPT-1 mRNA and protein levels(P<0.01) and Cyt-C protein level(P<0.01).Conclusion Up-regulation of lipid synthesis related genes and down-regulation of mitochondrial fatty acid β-oxidation related genes contribute to accelerated hepatic lipid accumulation induced by over-nutrition in lactating period.Over-nutrition in lactating period may be an important risk factor for non-alcoholic fatty acid liver disease in adults.[ACTA NUTRIMENTA SINICA,2012,34(6):540-544]