Genes related to the stress response, including heat-shock proteins (Hspa1a, Hsp90aa1, Dnajb1 and Hspa1b), AP1 transcription factor subunits (Fos and Jun), Egr1, VEGF receptor 2 (Kdr) and electron respiratory chain-related genes (mt-Atp6, mt-Co3, mt-Co2, mt-Nd2, mt-Nd1 and mt-Nd4) were downregulated in sustained obesity (cohort 2; Fig. 4e and Extended Data Fig. 9f). This evidence concerns the gene MT-CO3 and obesity due to melanocortin 4 receptor deficiency.