富生酮氨基酸饮食改善高脂诱导小鼠非酒精性脂肪肝  

Ketogenic essential amino acid replacement diet ameliorates nonalcoholic fatty liver disease in high-fat diet mice

作　　者：徐玲[1] 马红艳[1] 肖斌[2] 高陈林[1] 

机构地区：[1]泸州医学院附属医院内分泌代谢科,四川泸州646000 [2]四川医科大学基础医学院生物化学教研室,四川泸州646000

出　　处：《中国现代医学杂志》2016年第13期22-27,共6页China Journal of Modern Medicine

基　　金：四川省卫生厅科研基金(No:120330)

摘　　要：目的探讨富生酮氨基酸(KAA)饮食对高脂诱导小鼠非酒精性脂肪肝的影响及机制。方法 C57BL雄性小鼠随机分4组,给予常规饮食(NC)、高脂饮食(HFD)、富生酮氨基酸高脂饮食(HFD^(KAAR))以及高脂喂养8周后改为富生酮氨基酸高脂饮食(HFD→HFD^(KAAR))喂养。每周测进食量、体重,16周后行腹腔内注射葡萄糖耐量实验后处死小鼠,测肝重量、内脏脂肪重量、肝脂质沉积、Kupffer细胞聚集及肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)m RNA表达。结果各组小鼠摄入热卡比较差异无统计学意义。与NC组比较,HFD组小鼠体重和内脏脂肪重量增加,伴随胰岛素抵抗,肝脂质沉积和Kupffer细胞数量显著增加,TNF-α和IL-1βm RNA表达增加(P<0.05)。与HFD组比较,HFD^(KAAR)及HFD→HFD^(KAAR)组小鼠体重、内脏脂肪下降,胰岛素抵抗均减轻(P<0.05),肝脏Kupffer细胞的数量及脂质沉积减少,TNF-α和IL-1βm RNA的高表达均被逆转(P<0.05)。结论高脂膳食能诱导出非酒精性脂肪肝小鼠模型,富生酮氨基酸饮食可抑制高脂诱导的肝脏Kupffer细胞的表达,显著改善高脂饮食诱导的肥胖、胰岛素抵抗、肝脂质沉积,减轻肝脏的炎症损伤。Objective To reveal the effects of ketogenic amino acid（KAA） replacement diet in the high-fat diet-induced nonalcoholic fatty liver disease in mice. Methods C57 BL male mice were randomly fed with a conventional diet（NC group）, high-fat diet（HFD group） or KAA-fortified HFD（HFDKAAR group）; and 8weeks after HFD initiation, the HFD-fed mice were randomly divided into two groups： one group of mice was fed the same HFD, the other group was fed HFDKAAR（HFD →HFDKAAR）. The metabolic status and biochemical evaluations were performed 16 weeks after the initiation of experimental food. Blood glucose was measured by intraperitoneal glucose tolerance test. Insulin levels in plasma were measured using ELISA, the insulin resistance index（IRI） and area under curve（AUC） were calculated. The mesenteric and epididymal fat tissues and liver were weighed. Frozen liver sections were used for evaluation of hepatic steatosis and accu-mulation of Kupffer cells labeled by f4/80 via Oil Red O staining and immunofluorescence method respectively.The expressions of TNF-α and IL-1β m RNA were measured by real-time q PCR. Results All the mice ate almost similar calories. Compared to the NC group, the HFD-fed mice displayed significantly heavier body weight and intra-abdominal fat weight, severer hepatic steatosis, deterioration of glucose tolerance, and significantly-enhanced macrophage accumulation in liver; interestingly, these changes were reversed after rich-KAA diet administration. Furthermore, real-time q PCR showed hepatic TNF-α and IL-1β m RNA expressions were up-regulated in the HFD fed mice（P〈0.05）, these changes were dramatically ameliorated by taking rich-KAA diet（P〈0.05）. Conclusions Our data demonstrate that rich-KAA diet could significantly ameliorate HFDinduced hepatic steatosis, obesity and glucose intolerance via normalizing the macrophage accumulation. KAA replacement diet could be a potential nutritional intervention for treatment in patients with metabolic defects.

关 键 词：氨基酸 非酒精性脂肪肝病 代谢综合征 

分 类 号：R589.2[医药卫生—内分泌]