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Abdelkarim M et al .. Figure 1

FXR -/- + RSG. FXR +/+ + RSG. 250 µm. 250 µm. A. Weight of BAT. 0.7. Control. 0.6. **. RSG. ***. 0.5. 0.4. Weight (g). 0.3. C. 0.2. 0.1. 0. FXR +/+. FXR -/-. B. FXR +/+ - Control. 20. FXR +/+ + RSG. 15. Adipocyte fraction (%). 10. 5. 0. FXR -/- - Control. 20.

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Abdelkarim M et al .. Figure 1

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  1. FXR -/- + RSG FXR+/+ + RSG 250 µm 250 µm A Weight of BAT 0.7 Control 0.6 ** RSG *** 0.5 0.4 Weight (g) 0.3 C 0.2 0.1 0 FXR+/+ FXR -/- B FXR+/+ - Control 20 FXR+/+ + RSG 15 Adipocyte fraction (%) 10 5 0 FXR-/- - Control 20 FXR-/- + RSG 15 Adipocyte fraction (%) 10 5 0 0-20 40-60 20-40 60-80 80-100 140-160 160-180 180-200 100-120 120-140 Abdelkarim M et al.. Figure 1 Adipocyte diameter (µm)

  2. A Adiponectin CD36 LPL aP2 * 5 5 *** 4 8 *** Control *** 7 RSG 4 * 4 6 3 *** 5 3 3 mRNA/Cyclophilin 2 4 2 2 3 2 1 1 1 1 0 0 0 0 FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/- B C/EBPβ PPARγ C/EBPα ** * 6 2 6 Control RSG 5 5 ** 4 4 * mRNA/Cyclophilin 3 1 3 2 2 1 1 0 0 0 FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/- C ADRP S3-12 PERILIPIN FSP27 *** *** 8 4 4 4 Control 7 RSG * 6 3 3 3 5 mRNA/Cyclophilin 2 4 2 2 3 2 1 1 1 1 0 0 0 0 FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/- Abdelkarim M et al.. Figure 2

  3. - - - - - - - - + + + + + + + + D4 D4 D4 D4 D8 D8 D8 D8 FXR+/+ FXR+/+ FXR+/+ FXR+/+ FXR-/- FXR-/- FXR-/- FXR-/- C/EBPβ C/EBPα 120 8 * 7 100 6 80 5 mRNA /Cyclophilin 4 60 * 3 40 2 * * 20 1 0 0 RSG PPARγ aP2 50 1200 ** ** 1000 40 800 * 30 mRNA /Cyclophilin 600 * 20 400 * 10 200 * 0 0 RSG Days of Differentiation Abdelkarim M et al.. Figure 3

  4. lipogenesis de novo 30 * +/+ FXR +/+ FXR +/+ +/+ FXR FXR - / - FXR - / - FXR - - / / - - FXR FXR 25 protein incorporation 20 ) / mg 15 4 x10 10 Acetate ** dpm 5 ( D0 D4 D8 Days of differentiation +/+ FXR +/+ FXR - / - FXR - / - FXR 8 6 4 2 0 +/+ +/+ FXR FXR - / - - / - FXR FXR A TG content Lipolysis lipogenesis de novo 80 80 30 30 * * * +/+ +/+ +/+ +/+ FXR +/+ +/+ FXR FXR 18 - - / / - - - - / / - - FXR 70 70 - - / / - - FXR FXR 25 25 16 protein protein protein protein 60 60 protein ** 14 incorporation incorporation 20 20 50 50 12 /mg /mg ) / mg ) / mg 10 40 40 15 15 8 4 4 mg TG / mg *** 30 30 glycerol glycerol x10 x10 10 10 6 Acetate Acetate 20 20 ** ** 4 g g dpm dpm 5 5 µ µ 10 10 2 ( ( D0 D0 D4 D4 D8 D8 D4 D8 D0 D4 D8 D8+ISO D4+ISO Days of differentiation Days of differentiation C C B B PERILIPIN ADRP Size distribution of lipid 5000 16 * * +/+ +/+ +/+ +/+ FXR * * droplets 14 - - / / - - - - / / - - 4000 12 6000 ** 10 +/+ +/+ FXR 3000 mRNA/Cyclophilin mRNA/Cyclophilin ) ) 8 8 5000 - - / / - - FXR 2 2 m m 2000 6 6 µ µ 4 4 4000 1000 * * 2 2 0 0 0 3000 D0 D0 D2 D2 D4 D4 D8 D8 D0 D0 D2 D2 D4 D4 D8 D8 Cumulated area ( Cumulated area ( * S3 S3 - - 12 12 FSP27 FSP27 2000 350 350 30000 30000 * * +/+ +/+ +/+ +/+ ** ** FXR FXR 300 300 - - / / - - - - / / - - FXR FXR 25000 25000 * 1000 1000 * 250 250 20000 20000 * * 200 200 0 mRNA/Cyclophilin mRNA/Cyclophilin 15000 15000 150 150 2 2 2 2 2 2 2 2 2 m m m m m µ µ µ µ µ µ µ µ 10000 10000 6 80 100 100 18 <3 - - >80 - - 3 - 6 18 5000 5000 50 50 Range of area 0 0 0 0 D0 D0 D2 D2 D4 D4 D8 D8 D0 D0 D2 D2 D4 D4 D8 D8 Days of differentiation Days of differentiation Abdelkarim M et al.. Figure 4

  5. A aP2 aP2 PPAR PPAR C/ C/ EBP EBP C/ C/ EBP EBP 10 10 200 200 6 6 900 900 +/+ +/+ FXR FXR +/+ +/+ FXR FXR +/+ +/+ FXR FXR +/+ +/+ FXR FXR * * *** *** 800 800 ** ** * * * * - - / / - - FXR FXR - - / / - - FXR FXR - - / / - - FXR FXR - - / / - - FXR FXR 5 5 8 8 160 160 700 700 /Cyclophilin /Cyclophilin 4 4 600 600 6 6 120 120 500 500 3 3 * * 400 400 4 4 80 80 2 2 300 300 mRNA mRNA 200 200 40 40 2 2 1 1 100 100 0 0 0 0 0 0 0 0 D8 D8 D0 D0 D4 D4 D0 D0 D4 D4 D8 D8 D0 D0 D4 D4 D8 D8 D0 D0 D4 D4 D8 D8 Days of differentiation B C ADRP ADRP PERILIPIN PERILIPIN +/+ +/+ FXR FXR 600 600 30 30 +/+ +/+ +/+ +/+ FXR FXR FXR FXR - - / / - - FXR FXR - - / / - - FXR FXR 500 500 25 25 400 400 20 20 /Cyclophilin /Cyclophilin 300 300 15 15 * * 200 200 10 10 mRNA mRNA 100 100 5 5 0 0 0 0 D0 D0 D4 D4 D8 D8 D0 D0 D4 D4 D8 D8 - - / / - - FXR FXR FSP27 FSP27 S3 S3 - - 12 12 200 200 1000 1000 +/+ +/+ FXR FXR +/+ +/+ FXR FXR * * - - / / - - FXR FXR - - / / - - FXR FXR 800 800 150 150 /Cyclophilin /Cyclophilin 600 600 100 100 400 400 50 50 * * mRNA mRNA 200 200 Day 0 Day 0 Day 8 Day 8 0 0 0 0 D0 D0 D4 D4 D8 D8 D0 D0 D4 D4 D8 D8 Days of differentiation Days of differentiation Abdelkarim M et al.. Figure 5

  6. * C/EBPβ B A C/EBPα 7 30 * FXR-/- MEFs + empty retrovirus * 6 25 5 20 4 *** mRNA/Cyclophilin 15 3 * 10 2 5 1 0 0 PPAR aP2 * 1200 FXR-/- MEFs + FXR retrovirus 100 FXR+/+ +empty retrovirus 90 ** FXR-/- +empty retrovirus 1000 80 ** FXR-/- +FXR retrovirus 70 800 60 mRNA/Cyclophilin 600 50 40 ** 400 30 ** 20 ** 200 10 Day 8 0 0 D0 D2 D4 D0 D2 D4 D8 D8 Days of differentiation Days of differentiation C PERILIPIN ADRP * 16 140 ** *** FXR+/+ +empty retrovirus 14 120 FXR-/- +empty retrovirus FXR-/- +FXR retrovirus 12 *** 100 10 80 8 *** mRNA/Cyclophilin 60 ** 6 * 40 4 20 2 0 0 FSP27 S3-12 30 20000 * 25 * 15000 20 *** *** * mRNA/Cyclophilin 15 10000 * 10 5000 5 0 0 D0 D2 D4 D0 D2 D4 D8 D8 Days of differentiation Days of differentiation Abdelkarim M et al.. Figure 6

  7. 4 FXR FXR FXR FXR +/+ +/+ +/+ +/+ FXR FXR FXR FXR - - - - / / / / - - - - * 3 2 1 FXR FXR +/+ +/+ FXR FXR - - / / - - 0 FXR+/+ FXR-/- 4 c-Myc Axin2 LRP5 * ** 3 * * ** 2 1 0 A B C β-catenin sFRP1 sFRP5 20 20 6 6 * * * * -catenin protein 5 5 +/+ +/+ - - / / - - 15 15 FXR FXR FXR FXR Cyclophilin Cyclophilin 4 4 -catenin 10 10 3 3 mRNA/Cyclophilin c.i. c.i. acid acid 2 2 mRNA/ mRNA/ 5 5 red red D0 D2 D4 D8 D0 D2 D4 D8 D0 D2 D4 D8 D0 D2 D4 D8 1 1 Days of differentiation 0 0 0 0 D0 D0 D1 D1 D2 D2 D4 D4 D8 D8 D0 D0 D1 D1 D2 D2 D4 D4 D8 D8 Days of differentiation D E c-Myc LRP5 LRP5 Axin2 -catenin 5 * 8 8 4 6 6 ** *** * c.i. c.i. acid acid 7 7 5 5 4 * red red * * 6 6 3 FXR +/+ -/- -/- Cyclophilin Cyclophilin 4 4 5 5 3 Empty retrovirus mRNA/Cyclophilin 4 4 3 3 + + - 2 2 3 3 FXR retrovirus 2 2 mRNA/ mRNA/ - - + 2 2 1 1 1 1 1 1 0 0 0 0 0 0 D1 D1 D2 D2 D0 D0 D4 D4 D4 D4 D0 D8 D8 D1 D2 D8 D8 FXR+/+ FXR-/- FXR+/+ FXR-/- Cyclin D1 Axin2 Cyclin c-Myc 4 ** 4 5 5 3 3 *** Cyclophilin Cyclophilin 4 4 * 3 3 Cyclophilin Cyclophilin * 2 2 3 3 * mRNA/Cyclophilin 2 2 mRNA/ mRNA/ 2 2 1 1 mRNA/ mRNA/ 1 1 1 1 0 0 0 0 0 0 +/+ -/- -/- +/+ -/- -/- +/+ -/- -/- FXR FXR+/+ FXR-/- D0 D8 D1 D2 D4 FXR+/+ FXR-/- D1 D2 D4 D0 D8 Empty retrovirus + + - + + - + + - Days of differentiation FXR retrovirus - - + - - + - - + Abdelkarim M et al.. Figure 7 Abdelkarim M et al.. Figure 7

  8. A B 4 aP2 PPAR  3.5 ** 3 - catenin 2.5 c.i. c.i. acid red red 2 ** 1.5 -/- -/- -/- +/+ * +/+ FXR sFRP1 1 - - - - + 0.5 D0 D4 0 Days of differentiation +/+ -/- -/- +/+ -/- -/- FXR sFRP1 - - + - - + Abdelkarim M et al.. Figure 8

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