| First Author | Wan Z | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 12 | Pages | e51233 |
| PubMed ID | 23240005 | Mgi Jnum | J:195675 |
| Mgi Id | MGI:5484998 | Doi | 10.1371/journal.pone.0051233 |
| Citation | Wan Z, et al. (2012) IL-6 is not necessary for the regulation of adipose tissue mitochondrial content. PLoS One 7(12):e51233 |
| abstractText | BACKGROUND: Adipose tissue mitochondria have been implicated as key mediators of systemic metabolism. We have shown that IL-6 activates AMPK, a mediator of mitochondrial biogenesis, in adipose tissue; however, IL-6(-/-) mice fed a high fat diet have been reported to develop insulin resistance. These findings suggest that IL-6 may control adipose tissue mitochondrial content in vivo, and that reductions in adipose tissue mitochondria may be causally linked to the development of insulin resistance in IL-6(-/-) mice fed a high fat diet. On the other hand, IL-6 has been implicated as a negative regulator of insulin action. Given these discrepancies the purpose of the present investigation was to further evaluate the relationship between IL-6, adipose tissue mitochondrial content and whole body insulin action. METHODOLOGY AND PRINCIPAL FINDINGS: In cultured epididymal mouse adipose tissue IL-6 (75 ng/ml) induced the expression of the transcriptional co-activators PGC-1alpha and PRC, reputed mediators of mitochondrial biogenesis. Similarly, IL-6 increased the expression of COXIV and CPT-1. These effects were absent in cultured subcutaneous adipose tissue and were associated with lower levels of GP130 and IL-6 receptor alpha protein content. Markers of mitochondrial content were intact in adipose tissue from chow fed IL-6(-/-) mice. When fed a high fat diet IL-6(-/-) mice were more glucose and insulin intolerant than controls fed the same diet; however this was not explained by decreases in adipose tissue mitochondrial content or respiration. CONCLUSIONS AND SIGNIFICANCE: Our findings demonstrate depot-specific differences in the ability of IL-6 to induce PGC-1alpha and mitochondrial enzymes and demonstrate that IL-6 is not necessary for the maintenance of adipose tissue mitochondrial content in vivo. Moreover, reductions in adipose tissue mitochondria do not explain the greater insulin resistance in IL-6(-/-) mice fed a high fat diet. These results question the role of adipose tissue mitochondrial dysfunction in the etiology of insulin resistance. |
