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

• Published in: Cellular and molecular neurobiology Vol. 38; no. 1; pp. 349 - 361
• Main Authors: Vargovic, P., Laukova, M., Ukropec, J., Manz, G., Kvetnansky, R.
• Format: Journal Article
• Language: English
• Published: New York Springer US 2018; Springer Nature B.V
• Subjects: Adiponectin; Adipose tissue; Adipose tissue (brown); Adipose Tissue, Brown - immunology; Adipose Tissue, Brown - metabolism; Animals; Biomedical and Life Sciences; Biomedicine; Catecholamines; Cell Biology; Cold; Cold Temperature; Eotaxin; Gene expression; Hydroxylase; Immobilization; Immune response; Immunomodulation; Immunomodulation - physiology; Inflammation; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Interleukin 1; Interleukin 10; Interleukin 13; Interleukin 17; Interleukin 4; Interleukin 5; Interleukin 6; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - metabolism; Leukocytes (eosinophilic); Macrophages; Male; Methyltransferase; Monocyte chemoattractant protein 1; Monocytes; N-Methyltransferase; Neurobiology; Neurosciences; Norepinephrine; Original Research; Phenylethanolamine N-methyltransferase; Proteins; Rats; Rats, Sprague-Dawley; Rodents; Stress, Psychological - immunology; Stress, Psychological - metabolism; γ-Interferon; Adipose tissue; Uncoupling protein; Immobilization; Inflammatory mediators; Macrophages; Cold exposure; Heterotypic stressor
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-017-0531-z

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.