Prior Repeated Stress Attenuates Cold-Induced Immunomodulation Associated with "Browning" in Mesenteric Fat of Rats.
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.
['Vargovic|P|P|', 'Laukova|M|M|', 'Ukropec|J|J|', 'Manz|G|G|', 'Kvetnansky|R|R|']
D002001:Adipose Tissue, Brown D000818:Animals D003080:Cold Temperature D056747:Immunomodulation D018836:Inflammation Mediators D050152:Intra-Abdominal Fat D008297:Male D051381:Rats D017207:Rats, Sprague-Dawley D013315:Stress, Psychological
Adipose tissue Immobilization Cold exposure Uncoupling protein Macrophages Heterotypic stressor Inflammatory mediators