Abstract

IL-6 is a biologically active cytokine released during exercise by contracting skeletal muscles. It appears to be highly involved in the regulation of muscles energy substrate utilization. Whether an ablation of IL-6 (IL-6 KO) in mice subjected to a single bout of exercise affects lipid and/or glucose metabolism is currently unknown. In the present study we examined fatty acid (FAT/CD36, FABPpm, FATP-1, FATP-4) as well as glucose (GLUT-1, GLUT-4) transporters expression in IL-6 KO mice. In addition, intramuscular glycogen and lipid content was also evaluated. The expression of all fatty acid transporters (FAT/CD36: +25 %; FATP-1: +31 %; FABPpm: +12.7 %; FATP-4: +7.2 %) was increased in muscles from IL-6 KO mice compared to wild type (WT) mice. Accordingly intramuscular lipid content was also increased in these muscles (FFA: +38 %; DAG: +36 % and TAG: +160 %). Interestingly, IL-6 deficiency had only minor effect on glucose transporters expression (GLUT-1: −4 %, and GLUT-4: −5.1 %), with no apparent difference in muscular glycogen content. A single bout of exercise increased the glucose transporters (GLUT-1: +8 %; GLUT-4: +15 %) as well as FA transporters (FAT/CD36: +13 %; FABPpm: +4.5 %; FATP: +2.5 %, FATP-4: +10 %) expression but only in WT skeletal muscles. In muscles from IL-6 KO mice exercise induced changes only in glucose (GLUT-1: +20 %; GLUT-4: +35 %) but not in the content of FA transporters. Concomitantly, IL-6 KO mice displayed shorter time toward exhaustion with more pronounced reductions in intramuscular lipid and glycogen content. We may speculate, that IL-6 deficiency provokes more pronounced glucose utilization over lipid oxidation during a single bout of exhausting exercise.

Highlights

  • In the last few years, evidence has accumulated showing that interleukin-6 (IL-6) is an important molecule involvedLipids (2012) 47:763–772 in immune regulation, hematopoiesis or inflammation and in glucose and lipid metabolism [1]

  • The expression of all fatty acid transporters (FAT/CD36: ?25 %; FATP-1: ?31 %; FABPpm: ?12.7 %; FATP-4: ?7.2 %) was increased in muscles from IL-6 KO mice compared to wild type (WT) mice

  • The expression of fatty acid transporters (FAT/CD36: ?25 %; FABPpm: ?12.7 %; FATP1: ?31 %; p B 0.05; FATP-4: ?7.2 %; p [ 0.05) was increased in muscles from IL-6 KO mice compared to wild type mice (Fig. 1a–d)

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Summary

Introduction

In the last few years, evidence has accumulated showing that interleukin-6 (IL-6) is an important molecule involvedLipids (2012) 47:763–772 in immune regulation, hematopoiesis or inflammation and in glucose and lipid metabolism [1]. The resultant increase in IL-6 serum concentration positively correlates with increased glucose uptake and fatty acid (FA) oxidation in skeletal muscles. Both seem to be mediated by activation of AMPK (AMP-activated protein kinase) [1, 3, 4]. The activation of AMPK, which increases usage of energy substrates is commonly implicated in insulin sensitizing actions in skeletal muscles. This view has been recently challenged since serum IL-6 elevation was commonly observed in patients with metabolic disorders such as obesity and/or diabetes [5,6,7]. It might be speculated that IL-6 is a potent activator of SOCS (suppressor of cytokine signaling) and increased activation of SOCS3 in skeletal muscles and liver leads to insulin resistance commonly observed in patients with obesity and diabetes [8]

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