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在肥胖人群中,脂肪变性和非酒精性脂肪性肝炎中酮体生成有差异改变。

Ketone body production is differentially altered in steatosis and non-alcoholic steatohepatitis in obese humans.

机构信息

Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.

Department of Medicine, University of Helsinki, Helsinki and Minerva Medical Research Institute, Helsinki, Finland.

出版信息

Liver Int. 2015 Jul;35(7):1853-61. doi: 10.1111/liv.12769. Epub 2015 Jan 20.

DOI:10.1111/liv.12769
PMID:25533197
Abstract

BACKGROUND & AIMS: Levels of ketone bodies have been reported to be both increased and decreased in individuals with non-alcoholic fatty liver disease. We investigated whether the metabolism of ketone bodies is different in simple steatosis and in non-alcoholic steatohepatitis (NASH).

METHODS

Serum low molecular weight molecules including ketone bodies were measured using high-throughput proton (1H) nuclear magnetic resonance in 116 (76 categorized unequivocally to those with normal liver, simple steatosis or NASH) morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, body mass index 45.1 ± 6.1 kg/m(2) , 39 men and 77 women] with histological assessment of NASH and analysis of gene expression in the liver. Finally, we correlated β-hydroxybutyrate (β-OHB) levels with NASH predicting score in Metabolic Syndrome in Men Study (METSIM) population study (n = 8749 non-diabetic men).

RESULTS

Levels of ketone bodies were lower in individuals with NASH compared to individuals with simple steatosis (P = 0.004 and P = 0.018 for β-OHB and acetoacetate respectively). Lower levels of β-OHB were associated with the NASH predicting score in the METSIM study (P = 0.001). Liver inflammation correlated with mRNA expression of genes regulating ketolysis in the liver (Spearman correlation 0.379-0.388, P < 0.0006 for ACAT1, ACSS2 and BDH1).

CONCLUSION

Lower levels of ketone bodies in individuals with NASH compared to individuals with simple steatosis suggest a decrease in ketone body metabolism in NASH.

摘要

背景与目的

有报道称,非酒精性脂肪性肝病患者的酮体水平既升高又降低。我们研究了酮体代谢在单纯性脂肪变性和非酒精性脂肪性肝炎(NASH)中是否不同。

方法

使用高通量质子(1H)核磁共振技术测量 116 例(76 例明确分类为正常肝、单纯性脂肪变性或 NASH)病态肥胖个体(年龄 47.3±8.7 岁,平均±标准差;体重指数 45.1±6.1kg/m2;男性 39 例,女性 77 例)血清中低分子质量分子,包括酮体,并对 NASH 进行组织学评估和肝脏基因表达分析。最后,我们将β-羟丁酸(β-OHB)水平与代谢综合征男性研究(METSIM)人群研究(n=8749 例非糖尿病男性)中 NASH 预测评分相关联。

结果

与单纯性脂肪变性个体相比,NASH 个体的酮体水平较低(β-OHB 和乙酰乙酸分别为 P=0.004 和 P=0.018)。较低的β-OHB 水平与 METSIM 研究中的 NASH 预测评分相关(P=0.001)。肝脏炎症与调节肝脏酮分解的基因的 mRNA 表达呈正相关(Spearman 相关系数为 0.379-0.388,ACAT1、ACSS2 和 BDH1 的 P 值均<0.0006)。

结论

与单纯性脂肪变性个体相比,NASH 个体的酮体水平较低,表明 NASH 中酮体代谢减少。

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