Fig 2: Nrf2 transcription factor is involved in CD36 overexpression during inflammatory processes.CD36 mRNA level on Swiss peritoneal macrophages treated during 24 h with TNF-α (10 ng/mL) (A) and on RAW264.7 cells (B) and transfected with siRNA targeting Nrf2 (siRNA Nrf2) or control siRNA (siRNA control) and stimulated with sulforaphane SFN (10 µM) or diethylmaleate (DEM) (100 µM). Data are represented as a mean ± SD of three independent experiments. *p<0.05 and **p<0.01 compared with the respective control (cells transfected with siRNA control), (C) CD36 mRNA level on Nrf2+/+ and Nrf2−/− C57BL/6 murine peritoneal macrophages after treatment during 24 h with TNF-α and then incubated during 5 h with SFN or DEM. Data are from a representative experiment performed in triplicate ± SD. The experiment was repeated three times **p<0.01 compared with the respective control (Nrf2+/+), ##p<0.01 compared with the respective control (Nrf2+/+ cells treated with TNF-α). (D) Phagocytosis index of PfPEs by murine Nrf2+/+ and Nrf2−/− C57BL/6 macrophages stimulated as described in (C). Data are from a representative experiment performed in triplicate ± SD. The experiment was repeated three times. *p<0.05 and **p<0.01 compared with the respective control (Nrf2+/+ control cells); #p<0.05 compared with the respective control (Nrf2+/+ cells treated with TNF-α).

Fig 3: Nrf2 activators promote CD36 expression and enhance CD36-mediated PfPEs phagocytosis in inflammatory conditions.(A–B) CD36 protein and mRNA levels detected by flow cytometry or qRT-PCR on Swiss murine peritoneal macrophages firstly treated during 24 h with TNF-α (10 ng/mL), PGN (1 µg/mL) or P. falciparum culture (P.f. c s) and then incubated during 20 h with sulforaphane (SFN) (10 µM) or diethylmaleate (DEM) (100 µM) for protein quantification or 5 supplementary hours for mRNA detection. Data are represented as a mean ± SD of three independent experiments. **p<0.01 compared with the respective control (untreated); ##p<0.01 compared with the respective control (TNF-α treated cells); ¤¤p<0.01 compared with the respective control (PGN treated cells); §§p<0.01 compared with the respective control (P.f. cs treated cells); δδ p<0.01compared with control SFN-treated cells; ¶¶ p<0.01compared to control DEM-treated cells. (C) Phagocytosis index of Pf PEs by Swiss murine macrophages stimulated as described in (A). Data are represented as a mean ± SD of three independent experiments. *p<0.05 and **p<0.01 compared with the respective control (untreated); ##p<0.01 compared with the respective control (TNF-α treated cells); $$p<0.01 compared with the respective control (SFN treated cells); ££p<0.01 compared with the respective control (TNF+SFN treated cells) (D) HO-1 mRNA level in Swiss peritoneal macrophages determined by qRT-PCR after treatment of cells during 24 h with TNF-α (10 ng/mL) and then during 5 h with rosiglitazone (R) (5 µM), IL13 (50 ng/mL) or SFN (10 µM). Data are represented as a mean ± SD of three independent experiments. **p<0.01 compared with the respective control (untreated); ##p<0.01 compared with the respective control (TNF-α treated cells).

Fig 4: Nrf2 activators promote CD36 and increase P.falciparum clearance by human MDMs in inflammatory conditions.(A) CD36 protein level detected by flow cytometry on human-monocytes derived macrophages (hMDMs) firstly treated during 24 h with TNF-α (10 ng/mL) or PGN (1 µg/mL) and then incubated during 20 h with rosiglitazone (R) (5 µM), IL13 (50 ng/mL), SFN (10 µM) or DEM (100 µM). Data are represented as a mean ± SD of three independent experiments. **p<0.01 compared with the respective control (untreated); #p<0.05 compared with the respective control (TNF-α treated cells); ¤¤p<0.01 compared with the respective control (PGN treated cells). (B) PPARγ protein and mRNA levels on hMDMs treated with TNF-α, LPS, P.f. cs and PGN. PPARγ western blot is representative of three independent experiments and qPCR data are represented as a mean ± SD of three independent experiments. **p<0.01 compared with the respective control (untreated). (C) Phagocytosis index of P. falciparum unopsonized erythrocytes by hMDMs stimulated as described in (A). Data are represented as a mean ± SD of three independent experiments. **p<0.01 compared with the respective control (untreated); ##p<0.01 compared with the respective control (PGN treated cells); $$p<0.01 compared with the respective control (SFN treated cells); ££p<0.01 compared with the respective control (TNF+SFN treated cells).

Fig 5: Western blots of total GLUT4 (A, B) and FAT/CD36 (C, D) protein content from whole red (A, C) and white (B, D) gastrocnemius muscle. Data are expressed relative to WT‐Sed group, mean ± SE, n = 8–10. Experimental groups not sharing a letter are significantly different, P < 0.05. WT‐Sed, wild‐type+no exercise; WT‐Ex, wild‐type+exercise training; AdKO‐Sed, Ad knockout+no exercise; Ad‐Ex, Ad knockout+exercise training.