Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia

Sandrine Visentin (1) , Gérard Michel (2) , Claire Oudin (3) , Béatrice Cousin (4) , Benedicte Gaborit (5) , Ines Abdesselam (5) , Marie M. Maraninchi (5) , Marion Nowicki (5) , Rene Valero (5) , Maxime Guye (6) , Monique Bernard (6) , Pascal Auquier (7) , Hervé Chambost (8) , Marie-Christine Alessi (6, 5) , Sophie Béliard (9, 5)

1 Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM]
2 LGCIE - Laboratoire de Génie Civil et d'Ingénierie Environnementale
3 Centre Français des Porphyries
4 NPTME - Neurobiologie, plasticité tissulaire et métabolisme énergétique
5 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
6 CRMBM - Centre de résonance magnétique biologique et médicale
7 CEReSS - Centre d'études et de recherche sur les services de santé et la qualité de vie
8 Service de pédiatrie spécialisée et médecine infantile (neurologie, pneumologie, maladies héréditaires du métabolisme) [Hôpital de la Timone - APHM]
9 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases

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. Design: 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 1 H-spectroscopy. Functional characteristics of subcutaneous AT were investigated by studying gene expression and pre-adipocyte differentiation in culture. Results: Patients who have received TBI exhibited a lower BMI (minus 5 kg/m 2) and a lower waist circumference (minus 14 cm), especially irradiated women. Despite the lower quantity of intra-abdominal AT, irradiated patient displayed a nearly twofold 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. Conclusions: 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.

Mots clés: hepatic steatosis; adipocytes; irradiation; childhood AL; metabolic syndrome; ectopic fat

Domaines: Sciences du Vivant [q-bio]

Sandrine Visentin, Gérard Michel, Claire Oudin, Béatrice Cousin, Benedicte Gaborit, et al.. Lipodystrophy-like features after total body irradiation among survivors of childhood acute leukemia. Endocrine Connections, 2019, 8 (4), pp.349-359. ⟨10.1530/EC-18-0497⟩. ⟨hal-02337018⟩