Rossi Alessandro, Assunto Antonia, Rosano Carmen, Tucci Sara, Ruoppolo Margherita, Caterino Marianna, Pirozzi Francesca, Strisciuglio Pietro, Parenti Giancarlo, Melis Daniela
Department of Translational Medicine, Section of Pediatrics, University of Naples Federico II, Naples, Italy.
Pharmacy, Medical Center - University of Freiburg, Hugstetterstr. 55, D-79106, Freiburg, Germany.
Genes Nutr. 2023 Jun 6;18(1):10. doi: 10.1186/s12263-023-00729-y.
Glycogen storage disease type Ia (GSDIa) is an inborn metabolic disorder caused by the deficiency of glucose-6-phospatase-α (G6Pase-α) leading to mitochondrial dysfunction. It remains unclear whether mitochondrial dysfunction is present in patients' peripheral blood mononuclear cells (PBMC) and whether dietary treatment can play a role. The aim of this study was to investigate mitochondrial function in PBMC of GSDIa patients.
Ten GSDIa patients and 10 age-, sex- and fasting-time matched controls were enrolled. Expression of genes involved in mitochondrial function and activity of key fatty acid oxidation (FAO) and Krebs cycle proteins were assessed in PBMC. Targeted metabolomics and assessment of metabolic control markers were also performed.
Adult GSDIa patients showed increased CPT1A, SDHB, TFAM, mTOR expression (p < 0.05) and increased VLCAD, CPT2 and citrate synthase activity in PBMC (p < 0.05). VLCAD activity directly correlated with WC (p < 0.01), BMI (p < 0.05), serum malonycarnitine levels (p < 0.05). CPT2 activity directly correlated with BMI (p < 0.05).
Mitochondrial reprogramming is detectable in PBMC of GSDIa patients. This feature may develop as an adaptation to the liver enzyme defect and may be triggered by dietary (over)treatment in the frame of G6Pase-α deficiency. PBMC can represent an adequate mean to assess (diet-induced) metabolic disturbances in GSDIa.
Ia型糖原贮积病（GSDIa）是一种先天性代谢紊乱疾病，由葡萄糖-6-磷酸酶-α（G6Pase-α）缺乏导致线粒体功能障碍引起。目前尚不清楚患者外周血单个核细胞（PBMC）中是否存在线粒体功能障碍，以及饮食治疗是否能发挥作用。本研究的目的是调查GSDIa患者PBMC中的线粒体功能。
招募了10名GSDIa患者和10名年龄、性别和禁食时间匹配的对照者。评估PBMC中参与线粒体功能的基因表达以及关键脂肪酸氧化（FAO）和三羧酸循环蛋白的活性。还进行了靶向代谢组学分析和代谢控制标志物评估。
成年GSDIa患者PBMC中CPT1A、SDHB、TFAM、mTOR表达增加（p<0.05），VLCAD、CPT2和柠檬酸合酶活性增加（p<0.05）。VLCAD活性与腰围（p<0.01）、体重指数（p<0.05）、血清丙二酰肉碱水平（p<0.05）直接相关。CPT2活性与体重指数直接相关（p<0.05）。
在GSDIa患者的PBMC中可检测到线粒体重编程。这一特征可能是作为对肝脏酶缺陷的一种适应性变化而出现的，并且可能在G6Pase-α缺乏的情况下由饮食（过度）治疗引发。PBMC可以作为评估GSDIa中（饮食诱导的）代谢紊乱的合适手段。
