title: IL-6 is not necessary for the regulation of adipose tissue mitochondrial content.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Agriculture, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Zhongxiao
authors.initials: Z
authors.lastname: Wan
authors.forename: Christopher G R
authors.initials: CG
authors.lastname: Perry
authors.forename: Tara
authors.initials: T
authors.lastname: Macdonald
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Chan
authors.forename: Graham P
authors.initials: GP
authors.lastname: Holloway
authors.forename: David C
authors.initials: DC
authors.lastname: Wright
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology; D000818:Animals; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D051379:Mice; D063269:Mitochondrial Turnover / Q000235:genetics / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D007328:Insulin; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D005947:Glucose