IRX5 regulates adipocyte amyloid precursor protein and mitochondrial respiration in obesity.

Consistent with conserved obesity-related gene networks, we found a highly significant enrichment of Irx5-dependent mouse eWAT genes among the most differentially expressed genes in human adipocytes ( Figure 4A ), thereof 18 consistently up-regulated and 84 down-regulated genes in both the lean Irx5-KD mice and lean human patients ( Figure 4B ) (q-value < 0.05 in both datasets, genes with fold difference > 1.5 are shown in Table S1 ).

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In the beige-like ME3 cells, the effect of siRNA against App on maximal respiration and spare capacity was borderline significant ( Figure S2 ) whereas transient knock-down of Irx5 resulted in significant increase in maximal respiration ( p = 0.0011) and spare capacity p < 0.001) ( Figure S2 ).

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