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Permanent link (DOI): https://doi.org/10.7939/R32B8VR5K

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IL-6 is not necessary for the regulation of adipose tissue mitochondrial content Open Access

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Author or creator
Wan, Zhongxiao
Perry, Christopher G.
MacDonald, Tara
Chan, Catherine B.
Holloway, Graham P.
Wright, David C.
Additional contributors
Subject/Keyword
Biosynthesis
Fats
Insulin
Enzyme Regulation
Gene Expression
Insulin Resistance
Mitochondria
Adipose Tissue
Type of item
Journal Article (Published)
Language
English
Place
Time
Description
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-1α 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-1α 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.
Date created
2012
DOI
doi:10.7939/R32B8VR5K
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Attribution 4.0 International
Citation for previous publication
Wan, Z., Perry, C. G., MacDonald, T., Chan, C. B., Holloway, G. P., & Wright, D. C. (2012). IL-6 is not necessary for the regulation of adipose tissue mitochondrial content. PLoS ONE, 7(12), e51233 [10 pages].  http://dx.doi.org/10.1371/journal.pone.0051233

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