Alterations of body mass index and body composition in atomic bomb survivors

Tatsukawa, Yoshimi; Misumi, Munechika; Yamada, Michiko; Masunari, Naomi; Ōyama, Hiroshi; Nakanishi, Shuhei; Fukunaga, Masao; Fujiwara, Saeko

doi:10.1038/ijo.2012.193

Cited by 16 publications

(10 citation statements)

References 44 publications

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“…has also been reported that peripheral T cells in obese individuals are somewhat activated, displaying increased expression levels of surface CD25 (a subunit of the IL2 receptor) and polarization towards a pro-inflammatory type-1 (T H 1) phenotype (10)(11)(12). It should be noted here that metabolic abnormalities, including serum levels of high triglyceride, low HDL cholesterol and fatty liver development, have been reported in association with radiation dose among A-bomb survivors (13)(14)(15). Moreover, emerging evidence from mouse studies suggests direct interactions between diet-induced obesity and biological responses to radiation, e.g., DNA double-strand breaks, microRNA expression and cell survival (16,17).…”

Section: Introductionsupporting

confidence: 51%

Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors

Yoshida¹,

Nakashima²,

Kyoizumi³

et al. 2016

Radiation Research

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Immune system impairments reflected by the composition and function of circulating lymphocytes are still observed in atomic bomb survivors, and metabolic abnormalities including altered blood triglyceride and cholesterol levels have also been detected in such survivors. Based on closely related features of immune and metabolic profiles of individuals, we investigated the hypothesis that long-term effects of radiation exposure on lymphocyte subsets might be modified by metabolic profiles in 3,113 atomic bomb survivors who participated in health examinations at the Radiation Effect Research Foundation, Hiroshima and Nagasaki, in 2000-2002. The lymphocyte subsets analyzed involved T-, B- and NK-cell subsets, and their percentages in the lymphocyte fraction were assessed using flow cytometry. Health examinations included metabolic indicators, body mass index, serum levels of total cholesterol, high-density lipoprotein cholesterol, C-reactive protein and hemoglobin A1c, as well as diabetes and fatty liver diagnoses. Standard regression analyses indicated that several metabolic indicators of obesity/related disease, particularly high-density lipoprotein cholesterol levels, were positively associated with type-1 helper T- and B-cell percentages but were inversely associated with naïve CD4 T and NK cells. A regression analysis adjusted for high-density lipoprotein cholesterol revealed a radiation dose relationship with increasing NK-cell percentage. Additionally, an interaction effect was suggested between radiation dose and C-reactive protein on B-cell percentage with a negative coefficient of the interaction term. Collectively, these findings suggest that radiation exposure and subsequent metabolic profile changes, potentially in relationship to obesity-related inflammation, lead to such long-term alterations in lymphocyte subset composition. Because this study is based on cross-sectional and exploratory analyses, the implications regarding radiation exposure, metabolic profiles and circulating lymphocytes warrant future longitudinal and molecular mechanistic studies.

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Section: Introductionsupporting

confidence: 51%

Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors

Yoshida¹,

Nakashima²,

Kyoizumi³

et al. 2016

Radiation Research

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“…However, gender differences in the plasma metabolome have been reported (Trabado et al 2017). Gender differences in radiation damage and radiation-induced metabolic diseases have also been suggested but remain poorly defined (Tonorezos et al 2012;Tatsukawa et al 2013;Zhang et al 2014). Additionally, gender differences in the field of radiobiology, including ARS as well as the delayed effects of acute radiation exposure (DEARE) remain under-studied.…”

Section: Introductionmentioning

confidence: 99%

Effect of Sex on Biomarker Response in a Mouse Model of the Hematopoietic Acute Radiation Syndrome

et al. 2019

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Gender is an important confounding variable in biomarker development that must be incorporated into biomarker discovery and validation. Additionally, understanding of gender as a biological variable is essential for effective translation of biomarkers in animal models to human populations. Towards these ends, we conducted high-throughput targeted metabolomics using LC-MS/MS and multiplexed immunoassay analyses using a Luminex-based system in both male and female mice in a model of total-body irradiation at a radiation dose consistent with the hematopoietic acute radiation syndrome. Metabolomic and immunoassay analyses identified metabolites and cytokines that were significantly different in plasma from naïve and irradiated C57BL/6 mice consisting of equal numbers of female and male mice at 3 days after 8.0 or 8.72 Gy, an approximate LD60-70/30 dose of total-body irradiation. An additional number of metabolites and cytokines had gender-specific responses after radiation. Analyses in sham-irradiated mice illustrate the presence of stress-related changes in several cytokines due simply to undergoing the irradiation procedure absent actual radiation exposure. Basal differences in metabolite levels between female and male were also identified as well as time-dependent changes in cytokines up to 9 days post-exposure. These studies provide data toward defining the influence of gender on plasma-based biomarker candidates in a well-defined mouse model of acute radiation syndrome.

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“…There is little information regarding high-level radiation exposure-induced cachexia or muscle wasting. Studies on atomic bomb survivors 50 years after the event showed that atomic bomb radiation was associated significantly and negatively with body mass index and appendicular lean mass, even though the estimated radiation exposures were less than 4 Gy 29 . In the Chernobyl nuclear accident, patients presented with the typical hematological, cutaneous, gastrointestinal syndromes, and neurological/psychological disorders.…”

Section: Discussionmentioning

confidence: 99%

A non-human primate model of radiation-induced cachexia

Cui

Bennett

Zhang

et al. 2016

Sci Rep

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Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20–25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease.

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Alterations of body mass index and body composition in atomic bomb survivors

Abstract: This is the first study to report a significant dose response for BMI and body composition 50 years after A-bomb radiation exposure. We will need to conduct further studies to evaluate whether these alterations affect health status.

Cited by 16 publications

References 44 publications

Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors

Metabolic Profile as a Potential Modifier of Long-Term Radiation Effects on Peripheral Lymphocyte Subsets in Atomic Bomb Survivors

Effect of Sex on Biomarker Response in a Mouse Model of the Hematopoietic Acute Radiation Syndrome

A non-human primate model of radiation-induced cachexia

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