Fig. 3

Offspring of obese dams display an adapted hepatic stress response with an increased fatty acid oxidation. (a) Hallmark pathway gene set enrichment analysis (GSEA) of proteomics data obtained in early life (n = 5 per group). ‘Peroxisome’, ‘Angiogenesis’, ‘Fatty acid metabolism’ and ‘Oxidative phosphorylation’ pathways are significantly altered in offspring exposed to perinatal obesity (NES—normalized enrichment score). (b) The GSEA plot shows a downregulation of ‘Oxidative phosphorylation’ in the offspring. (c) The ‘Fatty acid metabolism’ gene set is upregulated in early life. (d) The GSEA plot of ‘peroxisome’ shows an increased NES in the offspring of obese dams. (e) Quantitative real-time PCR in early life and late adulthood of key regulators of fatty acid oxidation (FAO) display an altered FAO metabolism that persists into late adulthood (early life: SD n = 10, HFD n = 9; late adulthood: SD n = 7, HFD n = 9). (f) Over-representation analysis (ORA) of significantly upregulated proteins using the ‘Gene Ontology’ (GO) gene sets. ‘Fatty oxidation catabolic/ beta-oxidation’ is one of the most differentially regulated processes in offspring of perinatal obesity in early life. (g) The GSEA plot of the GO pathway ‘Fatty acid beta oxidation’ demonstrates an enriched gene set in offspring of perinatal obesity in early life. Data are presented as mean ± SEM. For proteomics analysis, GSEA and ORA were performed and p.adjust < 0.05 was considered statistically significant. For statistical analysis of PCR-results, T-test or Mann–Whitney U-test were applied and statistical significance was defined as p < 0.05 and marked as *.