Abstract
Skeletal muscle plays an important role in glycaemic control and metabolic homeostasis, making it a tissue of interest with respect to type 2 diabetes mellitus. The aim of the present study was to determine if ligands of Toll-like receptors (TLRs) could have an impact on energy metabolism and myokine expression and secretion in cultured human skeletal muscle cells. The myotubes expressed mRNA for TLRs 1–6. TLR3, TLR4, TLR5 and TLR6 ligands (TLRLs) increased glucose metabolism. Furthermore, TLR4L and TLR5L increased oleic acid metabolism. The metabolic effects of TLRLs were not evident until after at least 24 h pre-incubation of the cells and here the metabolic effects were more evident for the metabolism of glucose than oleic acid, with a shift towards effects on oleic acid metabolism after chronic exposure (168 h). However, the stimulatory effect of TLRLs on myokine expression and secretion was detected after only 6 h, where TLR3-6L stimulated secretion of interleukin-6 (IL-6). TLR5L also increased secretion of interleukin-8 (IL-8), while TLR6L also increased secretion of granulocyte–macrophage colony stimulating factor (GM-CSF). Pre-incubation of the myotubes with IL-6 for 24 h increased oleic acid oxidation but had no effect on glucose metabolism. Thus IL-6 did not mimic all the metabolic effects of the TLRLs, implying metabolic effects beyond the actions of this myokine.
Highlights
Skeletal muscle plays an important role in glycaemic control and metabolic homeostasis, making it a tissue of interest with respect to type 2 diabetes mellitus
While the Toll-like receptor 6 (TLR6) ligands (TLRLs) concentrations we have used in this study for most part are greater than physiological concentrations, we believe that taken together, our results show a proof of concept that TLRLs can exert effects on skeletal muscle metabolism
We have presented other effects of the TLRLs on energy metabolism in human myotubes, though we cannot exclude that these effects may be partly due to secretion of IL-6 or other myokines
Summary
Skeletal muscle plays an important role in glycaemic control and metabolic homeostasis, making it a tissue of interest with respect to type 2 diabetes mellitus. The metabolism of skeletal muscle is fuelled largely by carbohydrates and fatty acids, and it is a major insulin-sensitive organ, accounting for about 80% of the body’s insulin-stimulated glucose d isposal[2,3]. The critical role that skeletal muscle plays in glycaemic control and metabolic homeostasis makes it an organ of particular interest with regard to obesity and type 2 diabetes (T2D) mellitus. Amar and co-workers[17] have shown that following a week on a high-fat diet in mice, both adipose tissue and blood contained live commensals of the gut Both gram-negative and gram-positive bacteria, such as members of the genus Clostridium, have been suggested to have a role in the development of T2D. Clostridia were, for example, found to be more abundant in subjects with T2D than in healthy human individuals[18]
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