Role of IL-6 in Exercise Training- and Cold-Induced UCP1 Expression in Subcutaneous White Adipose Tissue

Expression of brown adipose tissue (BAT) associated proteins like uncoupling protein 1 (UCP1) in inguinal WAT (iWAT) has been suggested to alter iWAT metabolism. The aim of this study was to investigate the role of interleukin-6 (IL-6) in exercise training and cold exposure-induced iWAT UCP1 expression. The effect of daily intraperitoneal injections of IL-6 (3 ng/g) in C57BL/6 mice for 7 days on iWAT UCP1 expression was examined. In addition, the expression of UCP1 in iWAT was determined in response to 3 days of cold exposure (4°C) and 5 weeks of exercise training in wild type (WT) and whole body IL-6 knockout (KO) mice. Repeated injections of IL-6 in C57BL/6 mice increased UCP1 mRNA but not UCP1 protein content in iWAT. Cold exposure increased iWAT UCP1 mRNA content similarly in IL-6 KO and WT mice, while exercise training increased iWAT UCP1 mRNA in WT mice but not in IL-6 KO mice. Additionally, a cold exposure-induced increase in iWAT UCP1 protein content was blunted in IL-6 KO mice, while UCP1 protein content in iWAT was lower in both untrained and exercise trained IL-6 KO mice than in WT mice. In conclusion, repeated daily increases in plasma IL-6 can increase iWAT UCP1 mRNA content and IL-6 is required for an exercise training-induced increase in iWAT UCP1 mRNA content. In addition IL-6 is required for a full induction of UCP1 protein expression in response to cold exposure and influences the UCP1 protein content iWAT of both untrained and exercise trained animals

UCP1 and PGC-1α mRNA content in iWAT.

<p>UCP1 and PGC-1α mRNA in iWAT after 7 days of daily injection of IL-6 or PBS in C57BL/6 mice (A and B), in response to 3 days of cold exposure in WT and IL-6 KO mice (C and D) and in untrained and trained WT and IL-6 KO mice (E and F). The target mRNA is normalized to single stranded (ss) DNA or TBP mRNA content. Values are mean ± SE, (n = 6–12). *: significantly different from PBS or 22°C (p<0.05).</p

UCP1 protein Content in iWAT.

<p>iWAT UCP1 protein content after 7 days of daily injection of IL-6 or PBS in C57BL/6 mice (A), in untrained and trained WT and IL-6 KO mice (B), and in response to 3 days of cold exposure in WT and IL-6 KO mice (C). Representative blots from 7 days of daily injection of IL-6 or PBS in C57BL/6 mice (D), from untrained and trained WT and IL-6 KO mice (E) and from WT and IL-6 KO mice after 3 days of cold exposure (F). UCP1 antibody was verified with lysate from retinoblastoma deficient (RB −/−) differentiated to brown adipocytes cells and mouse iWAT (G). UCP1 protein content is normalized to β-actin protein content. Values are mean ± SE, (n = 6–12). #: significantly different from WT (p<0.05).*: significantly different from 22°C (p<0.05). A horizontal line indicates a main effect.</p