Article ; Online: Insulin resistance is associated with MCP1-mediated macrophage accumulation in skeletal muscle in mice and humans.
PloS one
2014 Volume 9, Issue 10, Page(s) e110653
Abstract: Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in ... ...
| Abstract | Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D. |
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| MeSH term(s) | Animals ; Cell Line ; Cell Movement ; Chemokine CCL2/physiology ; Diabetes Mellitus, Type 2/immunology ; Diabetes Mellitus, Type 2/metabolism ; Humans ; Insulin Resistance/immunology ; Macrophages/immunology ; Male ; Mice, Inbred C57BL ; Mice, Obese ; Mice, Transgenic ; Muscle, Skeletal/immunology ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Myositis/immunology ; Myositis/metabolism |
| Chemical Substances | Ccl2 protein, mouse ; Chemokine CCL2 |
| Language | English |
| Publishing date | 2014-10-22 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 1932-6203 |
| ISSN (online) | 1932-6203 |
| DOI | 10.1371/journal.pone.0110653 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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