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目的:检测ATP转运蛋白6(ATP binding cassette transporter A6,ABCA6)基因缺失对生酮饮食喂养的小鼠代谢的影响。方法:给予小鼠生酮饮食(ketogenic diet,KD)或普通饮食(normal diet,ND)2周,通过Western blot检测肝脏ABCA6的表达水平;给予ABCA6敲除(KO)小鼠或对照(WT)小鼠KD或ND 2周,检测小鼠的体重、血糖、血清甘油三酯(TG)、胆固醇(TCH)、游离脂肪酸(FFA)、酮体(β-HB)和转氨酶(AST、ALT)等指标,测定肝脏TG和TCH含量,并通过real-time PCR检测代谢相关基因的表达水平。结果:生酮饮食诱导小鼠肝脏ABCA6的表达;在普通饮食条件下,ABCA6 KO小鼠与对照小鼠在体重、血糖及血清TG、TCH、FFA、β-HB等代谢相关指标、肝脂质含量和代谢相关基因表达水平等方面无明显差别;在生酮饮食条件下,和WT小鼠相比,ABCA6 KO小鼠的血糖、FFA和TCH降低,肝脏TG蓄积更显著,肝脏FAS、DGAT2、PCK1和HMGCS2 mRNA显著增加。结论:ABCA6缺失引起小鼠对生酮饮食的代谢障碍,ABCA6可能参与肝脏的脂质代谢过程。
Objective: To investigate the effect of ABCA6 gene deletion on the metabolism of mice fed with ketogenic diet. Methods: The mice were fed with either ketogenic diet (KD) or normal diet (ND) for 2 weeks. The expression of ABCA6 in the liver was detected by Western blot. The mice were given ABCA6 knockout (KO) or control (WT) The body weight, blood glucose, serum triglyceride (TG), cholesterol (TCH), free fatty acid (FFA), ketone body (β-HB) and aminotransferase (AST, ALT) Indicators, determination of liver TG and TCH content, and by real-time PCR detection of metabolic-related gene expression levels. Results: Ketogenic diet induced the expression of ABCA6 in liver of mice. Under normal diet conditions, ABCA6 KO mice and control mice showed significant differences in body weight, blood glucose, serum TG, TCH, FFA and β-HB, There was no significant difference in the expression of genes related to metabolism, such as the level of FAS, DGAT2, PCK1 and HMGCS2 mRNA were significantly increased. CONCLUSION: ABCA6 deficiency causes metabolic disorders in ketogenic diet in mice. ABCA6 may be involved in the lipid metabolism of liver.