Visentin Sandrine, Michel Gérard, Oudin Claire, Cousin Béatrice, Gaborit Bénédicte, Abdesselam Inès, Maraninchi Marie, Nowicki Marion, Valéro René, Guye Maxime, Bernard Monique, Auquier Pascal, Chambost Hervé, Alessi Marie-Christine, Béliard Sophie
Department of Pediatric Hematology and Oncology, AP-HM, Timone Enfants Hospital, Marseille, France.
Aix Marseille University, INSERM, INRA, C2VN, Marseille, France.
Endocr Connect. 2019 Apr;8(4):349-359. doi: 10.1530/EC-18-0497.
BACKGROUND/OBJECTIVE: The number of long-term survivors of childhood acute leukemia (AL) is substantially growing. These patients are at high risk for metabolic syndrome (MS), especially those who received total body irradiation (TBI). The consequences of children's irradiation on adipose tissue (AT) development in adulthood are currently unknown. The objective of this study is to assess the impact of TBI on AT of childhood AL survivors.
We compared the morphological and functional characteristics of AT among survivors of childhood AL who developed MS and received (n = 12) or not received (n = 12) TBI.
SUBJECTS/METHODS: Body fat distribution and ectopic fat stores (abdominal visceral and liver fat) were evaluated by DEXA, MRI and 1H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture.
Patients who have received TBI exhibited a lower BMI (minus 5 kg/m2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly two-fold greater content of liver fat when compared to non-irradiated patient (17 vs 9%, P = 0.008). These lipodystrophic-like features are supplemented by molecular abnormalities in subcutaneous AT of irradiated patients: decrease of gene expression of SREBP1 (minus 39%, P = 0.01) and CIDEA (minus 36%, P = 0.004) and a clear alteration of pre-adipocyte differentiation.
These results strongly support the direct effect of irradiation on AT, especially in women, leading to specific nonalcoholic fatty liver disease, despite lower BMI. A long-term appropriate follow-up is necessary for these patients.
背景/目的：儿童急性白血病（AL）长期存活者的数量在大幅增加。这些患者患代谢综合征（MS）的风险很高，尤其是那些接受过全身照射（TBI）的患者。儿童期接受照射对成年期脂肪组织（AT）发育的影响目前尚不清楚。本研究的目的是评估TBI对儿童AL幸存者AT的影响。
我们比较了发生MS且接受（n = 12）或未接受（n = 12）TBI的儿童AL幸存者的AT的形态和功能特征。
对象/方法：通过双能X线吸收法（DEXA）、磁共振成像（MRI）和氢质子磁共振波谱（1H-光谱）评估身体脂肪分布和异位脂肪储存（腹部内脏脂肪和肝脏脂肪）。通过研究培养中的基因表达和前脂肪细胞分化来研究皮下AT的功能特征。
接受TBI的患者BMI较低（减去5kg/m²），腰围较小（减去14cm），尤其是接受照射的女性。尽管腹部AT数量较少，但与未接受照射的患者相比，接受照射的患者肝脏脂肪含量几乎高出两倍（17%对9%，P = 0.008）。这些脂肪营养不良样特征在接受照射患者的皮下AT分子异常中得到补充：固醇调节元件结合蛋白1（SREBP1）基因表达降低（减去39%，P = 0.01）和细胞死亡诱导DFFA样效应因子A（CIDEA）基因表达降低（减去36%，P = 0.004），以及前脂肪细胞分化明显改变。
这些结果有力地支持了照射对AT的直接影响，尤其是对女性，导致特定的非酒精性脂肪性肝病，尽管BMI较低。对这些患者进行长期适当的随访是必要的。
