Network analysis of adipose tissue gene expression highlights altered metabolic and regulatory transcriptomic activity in high-fat-diet-fed IL-1RI knockout mice
Citation:
Morine, M.J., Toomey, S., McGillicuddy, F.C., Reynolds, C.M., Power, K.A., Browne, J.A., Loscher, C., (...), Roche, H.M., Network analysis of adipose tissue gene expression highlights altered metabolic and regulatory transcriptomic activity in high-fat-diet-fed IL-1RI knockout mice, Journal of Nutritional Biochemistry, 24, 5, 2013, 788-795Download Item:
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.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
11/PI/1119
Science Foundation Ireland (SFI)
(06/IM.1/B105;
Irish Research Council for Science and Engineering Technology (IRCSET)
Author's Homepage:
http://people.tcd.ie/millskDescription:
PUBLISHED
Author: MILLS, KINGSTON
Type of material:
Journal ArticleCollections
Series/Report no:
Journal of Nutritional Biochemistry24
5
Availability:
Full text availableKeywords:
Adipose tissue, Insulin resistance, Network analysis, Transcriptomic profiling, IL-1 receptor type I, InflammationSubject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1016/j.jnutbio.2012.04.012Metadata
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