Journal Article


Helen M. Roche
Kingston H G Mills
Christine Loscher
John A Browne
Karen A Power
Clare M Reynolds
Fiona C McGillicuddy
Sinead Toomey
Melissa J Morine



diet high fat diabetes mellitus type 2 mice knockout network analysis il 1ri up regulation gene expression interleukin 1 il 1

Network analysis of adipose tissue gene expression highlights altered metabolic and regulatory transcriptomic activity in high-fat-diet-fed IL-1RI knockout mice. (2011)

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.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Helen M. Roche, Kingston H G Mills, Christine Loscher, John A Browne, Karen A Power, Clare M Reynolds, Fiona C McGillicuddy, Sinead Toomey, Melissa J Morine

Experts in our system

Helen M. Roche
University College Dublin
Total Publications: 105
Kingston Mills
Trinity College Dublin
Total Publications: 182
Christine E Loscher
Dublin City University
Total Publications: 32
John A Browne
University College Dublin
Total Publications: 73
Fiona C McGillicuddy
University College Dublin
Total Publications: 19
Sinead Toomey
Royal College of Surgeons in Ireland
Total Publications: 26