Ji et al. BMC Genomics 2012, 13:441 http://www.biomedcentral.com/1471-2164/13/441 Table 3 Shared effects of fasting and insulin-neutralization on differential gene expression Gene Gene title Fold change symbol Insu-Neu vs. Fed Up-regulated genes PDK4 pyruvate dehydrogenase kinase, isozyme 4 7.06 AOX1 aldehyde oxidase 1 2.94 PLEKHH2 pleckstrin homology domain containing, family H (with MyTH4 domain) member 2 2.41 FBXO8 F-box protein 8 2.09 AGTR1 angiotensin II receptor, type 1 2.04 PCMTD1 protein-L-isoaspartate (D-aspartate) O-methyltransferase domain containing 1 1.99 PSME4 proteasome (prosome, macropain) activator subunit 4 1.97 ICA1 islet cell autoantigen 1, 69 kDa 1.85 IP6K2 inositol hexakisphosphate kinase 2 1.77 UHRF2 ubiquitin-like, containing PHD and RING finger domains, 2 1.72 ACBD5 acyl-Coenzyme A binding domain containing 5 1.72 LOC417776 similar to hypothetical protein 1.62 CTSL2 cathepsin L2 1.54 ZNF217 zinc finger protein 217 1.54 IFNAR1 Interferon (alpha, beta and omega) receptor 1 1.52 Down-regulated genes DGAT2 diacylglycerol O-acyltransferase homolog 2 (mouse) 6.1 EEPD1 endonuclease/exonuclease/phosphatase family domain containing 1 2.4 ANKRD9 ankyrin repeat domain 9 2.19 DLST dihydrolipoamide S-succinyltransferase (E2 component of 2-oxo-glutarate complex 1.95 PTP4A3 protein tyrosine phosphatase type IVA, member 3 1.8 HSPA5 heat shock 70 kDa protein 5 (glucose-regulated protein, 78 kDa) 1.76 NOLA2 nucleolar protein family A, member 2 (H/ACA small nucleolar RNPs) 1.73 MST1R macrophage stimulating 1 receptor (c-met-related tyrosine kinase) 1.71 GRAMD2 GRAM domain containing 2 1.69 DHDDS dehydrodolichyl diphosphate synthase 1.63 DYNLL2 dynein, light chain, LC8-type 2 1.6 CDT1 chromatin licensing and DNA replication factor 1 1.57 FAHD1 fumarylacetoacetate hydrolase domain containing 1 1.56 DOT1L DOT1-like, histone H3 methyltransferase (S. cerevisiae) 1.56 BTBD11 BTB (POZ) domain containing 11 1.55 FDR p-value <0.05. Page 7 of 16 Fold change Fasting vs. Fed 17.28 6.66 2.77 4.15 4.15 2.25 3.86 2.8 2.75 1.89 2.51 1.84 2.09 2.6 3.47 10.5 2.17 1.98 1.76 2.3 1.74 1.57 2.2 2.37 1.58 2.52 1.51 1.61 1.82 1.71 insulin sensitivity [27]. Finally, a number of genes regu- lated by both fasting and insulin neutralization function in general processes related to protein synthesis. A total of thirteen genes (four up-regulated and nine down-regulated) were differentially expressed only with insulin neutralization (Table 4). The most interesting of these responses were upregulation of GCG, which encodes preproglucagon (fold change = 2.91), in parallel with down- regulation of the glucagon receptor (LOC425670, fold change = −2.77). Other genes uniquely affected by insulin have less clear relevance to adipose biology according to current knowledge. Tissue metabolomic analysis was used to identify the metabolic intermediates that were altered by fasting and insulin neutralization. A total of 92 metabolites were detected based on signal-to-noise ratios (Additional file 3). It is worth noting that glucose-6-phosphate content was similar in fasted or “diabetic” vs. fed status, despite a large range of plasma glucose levels (232–747 mg/100 ml). A total of 12 metabolites were significantly different between