Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine

Abstract

Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as 56Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of 56Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of 56Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract.

Ionizing Radiation-Induced Immune and Inflammatory Reactions in the Brain

“…At molecular level, long-term changes in DNA methylation patterns ( 149 ), distinctive miRNA signatures ( 150 ) were described in the brain following proton irradiation. Similar to γ-rays, heavy ion exposure also increased circulating leptin levels ( 151 ). It was reported by Baluchamy et al that high-energy protons induced a dose-dependent increase in reactive oxygen species and lipid peroxidation as well as a reduction in antioxidant levels in the brain, mainly in the neural stem cells, followed by apoptotic cell death ( 152 – 155 ).…”

Thoracic gamma irradiation-induced obesity in C57BL/6 female mice

“…Pulmonary radiationinduced gross metabolic abnormalities may be age-, physical status-, and dose-sensitive because populations with lung tumors are older, disease status, and use of fractionated dose regimes [$8 Gy]. female C57BL/6J mice that received a whole-body single exposure of 1.6 Gy 56Fe radiation (energy: 1000 MeV/n; LET: 148 keV/lm), which is equitoxic to 2 Gy of gamma radiation (Suman et al 2016), became overweight; Babbitt et al also found that young (weanling, 3 weeks) female C57BL/6 mice irradiated with four equal weekly cobalt-60 exposures (total cumulative doses: 3-5.1 Gy) (Babbitt et al 2001) had increased body weight. However, we found that female C57BL/6 mice exposed to 5 Gy TBI or 9 Gy sub-TBI did not become overweight, whereas mice exposed to 12.5 TRI did experience a significant increase in body weight.…”

“…Apart from carcinogenesis, radiation exposure has been related to obesity in humans (Sklar et al 2000;Oeffinger et al 2003;Ross et al 2004;Razzouk et al 2007) and animals (Babbitt et al 2001). Suman et al observed increased obesity-related factors 12 months after 56-Fe radiation exposure in female C57BL/6J mice (Suman et al 2016). Studies have shown genetic-related (Carter et al 1997;Fearnside et al 2008) and sex-related (Hwang et al 2010;Yang et al 2014) differences in dietinduced body weight increases in various mouse strains.…”

The Radio-mitigative Effect of CpG-Oligodeoxynucleotides on Mice After Exposure to Carbon Ions Radiation.

“…In the mouse studies, these bacterial challenges are non-toxic to normal mice. But under the conditions of heavy ions radiation, mice were morbidity or mortality [17][18][19]. Therefore, morbidity or mortality could be prevented by relieving I immune tissues injury.…”