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. 2019 Oct 25;7:248. doi: 10.3389/fcell.2019.00248

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Copyright © 2019 Knebel, Fahlbusch, Dille, Wahlers, Hartwig, Jacob, Kettel, Schiller, Herebian, Koellmer, Lehr, Müller-Wieland and Kotzka.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Upstream regulator molecules in peroxisomal proteins. All proteins identified in the peroxisomal fraction of C57Bl6 mice and alb-SREBP-1c mice were separated, according to overrepresentation in the genotypes, and subjected to IPA^® Core analyses. Upstream regulator molecule networks are shown for SREBP in C57Bl6 overrepresented proteins (A), or in alb-SREBP-1c overrepresented proteins (B) and for PPARa in C57Bl6 overrepresented proteins (C), or in alb-SREBP-1c overrepresented proteins (D). Hub molecules for SREBF1 in C57Bl6 mice were cholesterol, SCAP, Insulin, SREBF2, PPARG, PPARA, HIF1A, FOXO1, PPARGC1A, TP53, and RXRA. Hub proteins/molecules for SREBF1 in alb-SREBP-1c mice were SCAP, cholesterol, fatty acid, Ins1, PPARD, NR1H3, PPARG, PPARA, NR0B2, CEBPB, RXRA, SREBF2, NR5A2, NFE2L2, TP53, and PPARGC1A. Hub proteins/molecules for PPARA in C57Bl6 mice were bezafibrate, pirinixic acid, fenofibrate, NR1H4, PPARG, PPARD, NRIP1, RXRA, FOXO1, SREBF1, TP53, PPARGC1A, and NCOA2. Hub proteins/molecules for PPARA in alb-SREBP-1c mice were ciprofibrate, fenofibrate, pirinixic acid, NR1H4, PPARG, PPARD, MED1, NCOA2, NR1H3, FOXO1, RXRA, SREBF1, NR1I3, THRB, and PPARGC1A. Color code, according to IPA^® analyses, for molecules: green: overrepresented in alb-SREBP-1c (negative fold change in dataset); red: overrepresented in C57Bl6 (positive fold change in dataset), and for arrows: yellow: findings inconsistent with the state of the downstream molecule; blue: inhibition, consistent with the state of the downstream molecule; orange: increase, consistent with the state of the downstream molecule. Solid arrows indicate a direct interaction, and dotted arrows an indirect interaction, of connected molecules.