Abstract
Background:
Various pathogens are implicated in the induction of obesity. Previous studies have confirmed that human adenovirus 36 (Ad36) is associated with increased adiposity, improved glycemic control and induction of inflammation. The Ad36-induced inflammation is reflected in the infiltration of macrophages into adipose tissue. However, the characteristics and role of adipose tissue macrophages (ATMs) and macrophage-secreted factors in virus-induced obesity (VIO) are unclear. Although insulin-like growth factor-1 (IGF-1) is involved in obesity metabolism, the contribution of IGF secreted by macrophages in VIO has not been studied.
Methods:
Four-week-old male mice were studied 1 week and 12 weeks after Ad36 infection for determining the characteristics of ATMs in VIO and diet-induced obesity (DIO). In addition, macrophage-specific IGF-1-deficient (MIKO) mice were used to study the involvement of IGF-1 in VIO.
Results:
In the early stage of VIO (1 week after Ad36 infection), the M1 ATM sub-population increased, which increased the M1/M2 ratio, whereas DIO did not cause this change. In the late stage of VIO (12 weeks after Ad36 infection), the M1/M2 ratio did not change because the M1 and M2 ATM sub-populations increased to a similar extent, despite an increase in adiposity. By contrast, DIO increased the M1/M2 ratio. In addition, VIO in wild-type mice upregulated angiogenesis in adipose tissue and improved glycemic control. However, MIKO mice showed no increase in adiposity, angiogenesis, infiltration of macrophages into adipose tissue, or improvement in glycemic control after Ad36 infection.
Conclusions:
These data suggest that IGF-1 secreted by macrophages may contribute to hyperplasia and hypertrophy in adipose tissue by increasing angiogenesis, which helps to maintain the ‘adipose tissue robustness’.
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Acknowledgements
We thank Dr Anthony W Ferrante Jr from Columbia University for the gift of the MIKO mouse pair and Dr Yunhee Youm from Yale University for excellent guidance for the flow cytometry analysis. This work was supported by the Catholic University of Korea, Research Fund, 2015, by a grant from the Gyeonggi Regional Research Center of the Catholic University of Korea, by the Basic Science Research Program of the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012R1A1A2039819) and by a grant from the Korean Healthcare Technology R&D project of the Ministry of Health and Welfare (HI13C0826 and 2015M3A9B5030116).
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Park, S., Park, HL., Lee, SY. et al. Characteristics of adipose tissue macrophages and macrophage-derived insulin-like growth factor-1 in virus-induced obesity. Int J Obes 40, 460–470 (2016). https://doi.org/10.1038/ijo.2015.194
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DOI: https://doi.org/10.1038/ijo.2015.194
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