* * * * B A WT RORa hypo C WT RORa hypo D RORa hypo RORa hypo WAT Liver Brain Relative RORa expression B Relative RORa expression * * * C mg/dL WT RORa hypo D % of cell population % of cell population * RORa hypo RORa hypo Supplemental Fig.1: RORa deficient mice show an anti-inflammatory profile: A. RORa mRNA expression in white adipose tissue, liver and brain of males RORaWT (white bar, n=5) or RORaHypo (black bar, n=5). B. RORa mRNA expression in the intestine of males RORaWT (white bar, n=8) or RORaHypo (black bar, n=8) C. Weight, fat mass and lean mass of single housed 12 week-old males RORaWT (white bar, n=6) or RORaHypo (black bar, n=6)) littermate. C. CD4 (upper) or CD8 (lower) expression in lymph nodes freshly isolated from the 12 week-old male RORaWT (white, n=5) or RORaHypo (black, n=5) mice. *p<0,05.

Supplemental Fig.2: SR1001 does not impair macrophages polarization: Relative expression Supplemental Fig.2: SR1001 does not impair macrophages polarization: Gene expression from BMDM treated with SR1001 (10uM) during M2 (IL-4 treated) or M1 5INFg/LPS treated) polarization. n=9

Body weight (g) A ** mg/dL B % cell population CD4+ cells Vehicle SR1001 D U/L % cell population * E *** Supplemental Fig.3: SR1001 does not affect weight but decreases pro-inflammatory cells development in lymph nodes: Body weight and blood lipid profile of single housed males LDL-R-/- treated with SR1001 (white bar, n=9) or vehicle (black bar, n=9) after 10 days of HC diet before 30 days dosing. B. CD4 cells population in lymph nodes freshly isolated from the same animals. C. Body weight of single housed males LDL-R-/- treated with SR1001 (white bar, n=9) or vehicle (black bar, n=9) after a month of HC diet during 30 days dosing and D. Plasma liver enzyme level after 30 days dosing. E. Treg, Th1, Th2 and Th17 cells population in lymph nodes freshly isolated from the same animals. (n=6). *p<0,05; ***p<0,001.

Anti-body Clone CD3 17A2 CD4 GK1.5 CD8a 53-6.7 CD115 AFS98 B220 RA3-6B2 IL-17R 9B10 Ly6G 1A8 CD25 PC61 Foxp3 MF-14 INFg XMG1.2 Gata3 16E10A23 ABCG5 NBP1-59803 Supplemental Table1: List of anti-bodies used All the flow cytometry anti-bodies come from Biolegend and ABCG5 come from Novus Biologicals