title: Network analysis of adipose tissue gene expression highlights altered metabolic and regulatory transcriptomic activity in high-fat-diet-fed IL-1RI knockout mice.
abstract: A subacute inflammatory phenotype is implicated in the pathology of insulin resistance (IR) and type 2 diabetes mellitus. Interleukin (IL)-1α and IL-1β are produced by innate immune cells, including macrophages, and mediate their inflammatory response through the IL-1 type I receptor (IL-IRI). This study sought to understand the transcriptomic signature of adipose tissue in obese IL-1RI(-/-) mice. Following dietary intervention, markers of insulin sensitivity and inflammation in adipose tissue were determined, and gene expression was assessed with microarrays. IL-1RI(-/-) mice fed a high-fat diet (HFD) had significantly lower plasma inflammatory cytokine concentrations than wild-type mice. Metabolic network analysis of transcriptomic effects identified up-regulation and co-expression of genes involved in lipolysis, lipogenesis and tricarboxylic acid (TCA) cycle. Further assessment of gene expression in a network of protein interactions related to innate immunity highlighted Stat3 as a potential transcriptional regulator of IL-1 signalling. The complex, downstream effects of IL-1 signalling through the IL-1RI receptor remain poorly defined. Using network-based analyses of transcriptomic signatures in IL-1RI(-/-) mice, we have identified expression changes in genes involved in lipid cycling and TCA cycle, which may be more broadly indicative of a restoration of mitochondrial function in the context of HFD. Our results also highlight a potential role for Stat3 in linking IL-1 signalling to adipogenesis and IR.
authors: Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Dublin 4, Ireland.
authors: Melissa J
authors: MJ
authors: Morine
authors: Sinead
authors: S
authors: Toomey
authors: Fiona C
authors: FC
authors: McGillicuddy
authors: Clare M
authors: CM
authors: Reynolds
authors: Karen A
authors: KA
authors: Power
authors: John A
authors: JA
authors: Browne
authors: Christine
authors: C
authors: Loscher
authors: Kingston H G
authors: KH
authors: Mills
authors: Helen M
authors: HM
authors: Roche
mesh_terms: D000208:Acute Disease; D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002952:Citric Acid Cycle; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D015870:Gene Expression; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D007375:Interleukin-1 / Q000097:blood; D050155:Lipogenesis; D008264:Macrophages / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D046228:Microarray Analysis; D009765:Obesity / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse