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Prior Repeated Stress Attenuates Cold-Induced Immunomodulation Associated with “Browning” in Mesenteric Fat of Rats

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Abstract

Continuous exposure to cold leads to activation of adaptive thermogenesis in brown adipose tissue but also to induction of brown/beige cell phenotype in white adipose tissue. The aim of this work was to investigate whether prior exposure to immobilization (IMO) stress may affect immune response associated with adipocyte “browning” in mesenteric adipose tissue (mWAT). In the first experiment, Sprague–Dawley rats were exposed to acute (3 h) or prolonged (7 days) cold exposure (4 ± 1 °C). 7-day cold stimulated gene expression of uncoupling protein 1 and other “browning”-associated factors. In the second experiment, rats were immobilized for 7 days (2 h daily) followed by exposure to continuous cold for 1 or 7 days. Prior IMO exaggerated cold-induced sympathetic response manifested by elevated tyrosine hydroxylase (TH) protein and norepinephrine in mWAT. Induction of non-sympathetic catecholamine production demonstrated by elevated TH and PNMT (phenylethanolamine N-methyltransferase) mRNAs was observed after 7-day cold; however, prior IMO attenuated this response. 7-day cold-induced gene expression of anti-inflammatory mediators (IL-4, IL-13, IL-10, adiponectin), markers of M2 macrophages (Arg1, Retnlα), and eosinophil-associated molecules (eotaxin, IL-5), while inhibited expression of pro-inflammatory cytokines (IFNγ, IL-1b, IL-6, IL-17) and monocytes (MCP-1, Ly6C). This immune response was accompanied by elevated expression of uncoupling protein-1 and other thermogenic factors. Rats exposed to prior IMO exhibited inhibition of cold-induced immune and “browning”-related expression pattern. Overall, we demonstrated that 7-day cold-induced browning”-associated changes in rat mWAT, while prior history of repeated stress prevented this response.

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Acknowledgements

This research was supported by Slovak Research and Development Agency (No. APVV-0088-10); and VEGA Grant (2/0067/14).

Author’s Contribution

The authors’ responsibilities were as follow: R.K., P.V., and J.U. conceived and designed the study; P.V., G.M., and J.U. contributed to optimization of methods, sample and data collection and data analysis; P.V. and M.L. wrote the manuscript; P.V., M.L., J.U., R.K. researched data and contributed to the discussion. All authors reviewed and edited the manuscript.

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Authors and Affiliations

  1. Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 84505, Bratislava, Slovakia

    P. Vargovic, M. Laukova, J. Ukropec & R. Kvetnansky

  2. Department of Environmental Health Science, School of Health Sciences and Practice, Institute of Public Health, New York Medical College, Valhalla, NY, USA

    M. Laukova

  3. LDN Labor Diagnostica Nord, 48531, Nordhorn, Germany

    G. Manz

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  1. P. Vargovic
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Correspondence to P. Vargovic.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Institute of Experimental Endocrinology at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Vargovic, P., Laukova, M., Ukropec, J. et al. Prior Repeated Stress Attenuates Cold-Induced Immunomodulation Associated with “Browning” in Mesenteric Fat of Rats. Cell Mol Neurobiol 38, 349–361 (2018). https://doi.org/10.1007/s10571-017-0531-z

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