Abstract
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.
Highlights
Uncoupling protein 1 (UCP1) is primarily expressed in brown adipose tissue (BAT) and is central to the thermogenic function of the tissue [1]
The major findings of the present study are that a daily injection of IL-6 for 7 days increased UCP1 mRNA content in inguinal white adipose tissue (WAT) (iWAT), that IL-6 was required for the exercise training-induced increase in iWAT UCP1 mRNA and that the cold exposure-induced increase in UCP1 protein content observed in wild type (WT) mice was markedly reduced in IL-6 KO mice
The effect of exercise training on iWAT UCP1 mRNA content in WT mice observed in the present study is in agreement with previous studies showing increased iWAT UCP1 mRNA after both swimming and treadmill exercise training [8,9]
Summary
Uncoupling protein 1 (UCP1) is primarily expressed in brown adipose tissue (BAT) and is central to the thermogenic function of the tissue [1]. Expression of UCP1 in white adipose tissue (WAT) has been observed in response to treatment with a b3-adrenergic receptor agonist [2] and cold exposure [3].This has led to the suggestion that expression of BAT genes in WAT and concomitant browning of the tissue may alter WAT metabolism [4]. BAT UCP1expression is induced by cold exposure through activation of the sympathetic nervous system [5]. Expression of other BAT related genes such as cell death-inducing
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