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Volume 16, Issue 9, Pages (August 2016)

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1 Volume 16, Issue 9, Pages 2317-2326 (August 2016)
The Adipose Transcriptional Response to Insulin Is Determined by Obesity, Not Insulin Sensitivity  Mikael Rydén, Olga Hrydziuszko, Enrichetta Mileti, Amitha Raman, Jette Bornholdt, Mette Boyd, Eva Toft, Veronica Qvist, Erik Näslund, Anders Thorell, Daniel P. Andersson, Ingrid Dahlman, Hui Gao, Albin Sandelin, Carsten O. Daub, Peter Arner  Cell Reports  Volume 16, Issue 9, Pages (August 2016) DOI: /j.celrep Copyright © 2016 The Authors Terms and Conditions

2 Cell Reports 2016 16, 2317-2326DOI: (10.1016/j.celrep.2016.07.070)
Copyright © 2016 The Authors Terms and Conditions

3 Figure 1 Clamp Validation
(A) Individual M values are detailed for the NO, ISO, and IRO groups. ∗∗∗p < (B) Volcano plot of the 30,331 detected CAGE tag clusters, corresponding to 15,518 genes, expressed as log fold change fasting/hyperinsulinemia (f/hi) along the x axis and false discovery rate (FDR) on the y axis. In blue: 29,964 tag clusters (15,398 genes) responding to the clamp. In red: 367 tag clusters (122 genes) involved in the insulin signaling pathway. The eight tag clusters corresponding to eight genes involved in the insulin signaling pathway are highlighted. The horizontal line shows an FDR < 0.05. (C) Expression fold changes (fasting/hyperinsulinemia; f/hi) of the eight insulin signaling pathway genes shown in (B). (D) qPCR validation of selected genes from (C) in the NO group expressed as f/hi. Paired two-sided t tests gave p values between < and Cell Reports  , DOI: ( /j.celrep ) Copyright © 2016 The Authors Terms and Conditions

4 Figure 2 Overall Differences in Insulin-Induced Gene Expression among the NO, ISO, and IRO Groups (A) The number of differentially expressed CAGE tag clusters altered by fasting/hyperinsulinemia (f/hi) according to the way of comparison in Figure S1C. (B) Principal-component (PC) analysis plot summarizing the high-dimensional transcriptional data from (A) for NO, ISO, and IRO groups along PC1 and PC2, explaining the most variance in the data. Circles represent 95% confidence intervals. (C and D) Statistical analyses (t test) of group differences in (B) along PC1 (C) and PC2 (D). ∗∗p < 0.01; ∗∗∗p < 0.001; ns, not significant. See also Figure S1C. Cell Reports  , DOI: ( /j.celrep ) Copyright © 2016 The Authors Terms and Conditions

5 Figure 3 Identification of Genes Altered by Hyperinsulinemia in ISO and IRO Groups (A) Venn diagram of tag clusters and genes significantly altered by hyperinsulinemia in the ISO or IRO group. (B) Comparison between expression fold change (fasting/hyperinsulinemia; f/hi) of tag clusters common in ISO and IRO groups. (C) KEGG pathways to which insulin-responding genes from (A) are mapping. (D) Number of genes corresponding to genes in (A) after the PubMatrix filtering step described in Results. (E and F) Top differentially altered genes in the ISO (D) and IRO (E) groups. The y axis shows the expression fold change induced by insulin expressed as f/hi. Cell Reports  , DOI: ( /j.celrep ) Copyright © 2016 The Authors Terms and Conditions


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