(A) Multidimensional Scaling Plot showing distinct patterns of gene expression of interscapular tissue samples from P2 and P3, compared to five age-matched controls. Three separate tissue samples from each of the patients and two to three separate tissue samples from the controls were used in the analysis. (B) Bar chart showing the 10 most significantly altered pathways identified by Ingenuity Pathway Analysis (IPA). Canonical pathways are shown in red to indicate increased expression; non-canonical pathways, to which no directionality was assigned, are shown in grey. The red line represents the p-value cut-off of <0.0001. (C) Heat maps showing decreased expression of genes in the mitochondrial genome and increased expression of nuclear-encoded oxidative phosphorylation (OxPhos) genes in P2 and P3. (D) Immunoblots of control and patient adipose tissue for OXPHOS subunits ATP synthase subunit alpha (V), Complex III subunit Core 2 (III), Complex II subunit 30 kDa (II), and the mitochondrial marker citrate synthase (CS). TATA-binding protein (TBP) and β-actin (ACTB) levels were used as loading controls (as also shown in Figure 1H). (E) Reduced levels of mtDNA in affected adipose tissue determined by Taqman real-time PCR. Means of three independent experiments ± SEM are shown. (**p<0.01). (F) Increased expression of PGC1A, PGC1B, and NEF2L2 assessed by real-time qPCR and expressed as fold change in expression relative to five controls. Shown are means of 3 replicates. Error bars represent SEM. (G) Heat map showing the top 32 ‘disease and biology’ pathways from IPA. A word/tag weighted cloud of component pathways is shown. (H) Venn Diagrams comparing the top 100 genes up and down with an FDR cut-off of <0.00001 among patients. Genes shared between all three patients’ samples are shown in expanded lists with genes noted in the text highlighted in red. (I) Transcript levels of DDIT3, HSPA5, ATF5, TRIB3, PSAT1, and CIDEA in P3 and P2, expressed as fold change relative to controls determined by Taqman quantitative real-time PCR. Shown are means of eight replicates of different dilutions with error bars calculated from R-squared values of fitted line.