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

Shubhankar Suman,Santosh Kumar,Kamal Datta,Albert J Fornace

doi:10.1038/srep31853

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.

Highlights

On GI is important due to the fact that GI homeostasis is critical for astronauts’ nutrition during prolonged space missions
We demonstrate for the first time that exposure to a non-lethal dose (1.6 Gy) of energetic 56Fe ions led to increased serum insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and leptin levels at two and twelve months after radiation exposure
When compared with γradiation results, we observed that heavy ion radiation exposure was associated with higher body weight, and greater serum TG and insulin levels (Figure S1)

Summary

Introduction

On GI is important due to the fact that GI homeostasis is critical for astronauts’ nutrition during prolonged space missions. There is increasing evidence that leptin/IGF1 signaling cooperates to promote cellular proliferation and carcinogenesis, and altered metabolic/hormonal state and increased body weight[20,21,22,23,24,25,26] Both radiation exposure and metabolic/hormonal dysregulation have been linked to altered intestinal homeostasis and colorectal carcinogenesis[25,27,28,29,30,31,32,33,34]. When considered along with upregulated signaling pathways downstream of IGF1 and leptin, and increased proliferative markers and body weight in irradiated mice, our results are suggestive of increased risk for metabolic alterations and cancer in GI tract after energetic heavy ion radiation exposure

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Results

Conclusion