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

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          Abstract

          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 1H-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 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.

          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.

          Related collections

          Most cited references 29

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          Global physical activity questionnaire (GPAQ): nine country reliability and validity study.

          Instruments to assess physical activity are needed for (inter)national surveillance systems and comparison. Male and female adults were recruited from diverse sociocultural, educational and economic backgrounds in 9 countries (total n = 2657). GPAQ and the International Physical Activity Questionnaire (IPAQ) were administered on at least 2 occasions. Eight countries assessed criterion validity using an objective measure (pedometer or accelerometer) over 7 days. Reliability coefficients were of moderate to substantial strength (Kappa 0.67 to 0.73; Spearman's rho 0.67 to 0.81). Results on concurrent validity between IPAQ and GPAQ also showed a moderate to strong positive relationship (range 0.45 to 0.65). Results on criterion validity were in the poor-fair (range 0.06 to 0.35). There were some observed differences between sex, education, BMI and urban/rural and between countries. Overall GPAQ provides reproducible data and showed a moderate-strong positive correlation with IPAQ, a previously validated and accepted measure of physical activity. Validation of GPAQ produced poor results although the magnitude was similar to the range reported in other studies. Overall, these results indicate that GPAQ is a suitable and acceptable instrument for monitoring physical activity in population health surveillance systems, although further replication of this work in other countries is warranted.
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            Biology, risk stratification, and therapy of pediatric acute leukemias: an update.

            We review recent advances in the biologic understanding and treatment of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), identify therapeutically challenging subgroups, and suggest future directions of research. A review of English literature on childhood acute leukemias from the past 5 years was performed. Contemporary treatments have resulted in 5-year event-free survival rates of approximately 80% for childhood ALL and almost 60% for pediatric AML. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of leukemia. Virtually all ALL and the vast majority of AML cases can be classified according to specific genetic abnormalities. Cooperative mutations involved in cell differentiation, cell cycle regulation, tumor suppression, drug responsiveness, and apoptosis have also been identified in many cases. The development of new formulations of existing drugs, molecularly targeted therapy, and immunotherapies promises to further advance the cure rates and improve quality of life of patients. The application of new high-throughput sequencing techniques to define the complete DNA sequence of leukemia and host normal cells and the development of new agents targeted to leukemogenic pathways promise to further improve outcome in the coming decade.
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              Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance.

              Whereas truncal (central) adiposity is strongly associated with the insulin resistant metabolic syndrome, it is uncertain whether this is accounted for principally by visceral adiposity (VAT). Several recent studies find as strong or stronger association between subcutaneous abdominal adiposity (SAT) and insulin resistance. To reexamine the issue of truncal adipose tissue depots, we performed cross-sectional abdominal computed tomography, and we undertook the novel approach of partitioning SAT into the plane superficial to the fascia within subcutaneous adipose tissue (superficial SAT) and that below this fascia (deep SAT), as well as measurement of VAT. Among 47 lean and obese glucose-tolerant men and women, insulin-stimulated glucose utilization, measured by euglycemic clamp, was strongly correlated with both VAT and deep SAT (r = -0.61 and -0.64, respectively; both P < 0.001), but not with superficial SAT (r = -0.29, not significant). Also, VAT and deep SAT followed a highly congruent pattern of associations with glucose and insulin area under the curve (75-g oral glucose tolerance test), mean arterial blood pressure, apoprotein-B, high-density lipoprotein cholesterol, and triglyceride. Superficial SAT had markedly weaker association with all these parameters and instead followed the pattern observed for thigh subcutaneous adiposity. We conclude that there are two functionally distinct compartments of adipose tissue within abdominal subcutaneous fat and that the deep SAT has a strong relation to insulin resistance.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                April 2019
                07 March 2019
                : 8
                : 4
                : 349-359
                Affiliations
                [1 ]Department of Pediatric Hematology and Oncology , AP-HM, Timone Enfants Hospital, Marseille, France
                [2 ]Aix Marseille University , INSERM, INRA, C2VN, Marseille, France
                [3 ]Research Unit EA 3279 and Department of Public Health , Aix-Marseille University, Marseille, France
                [4 ]STROMALab , Université de Toulouse, CNRS ERL5311, EFS, INP-ENVT, INSERM U1031, UPS, Toulouse, France
                [5 ]Nutrition , Metabolic Diseases and Endocrinology Department, AP-HM, La Conception Hospital, Marseille, France
                [6 ]AP-HM , Timone, CEMEREM, Marseille, France
                [7 ]Aix-Marseille University , CNRS, CRMBM, Marseille, France
                Author notes
                Correspondence should be addressed to S Visentin: Sandrine.visentin@ 123456ap-hm.fr
                Article
                EC-18-0497
                10.1530/EC-18-0497
                6454302
                30844749
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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