8
Abdelkarim M et al.. Figure B A Weight of BAT Weight (g) FXR +/+ FXR -/- 0 0.1 0.2 0.3 0.4 0.5 0.6 ** *** 0.7 Control RSG Adipocyte diameter (µm) Adipocyte fraction (%) 0 5 10 15 20 0-20 20-40 40-60 60-80 80-100 100-120 120-1 4 0 140-160 160-180 180-200 0 5 10 15 20 Adipocyte fraction (%) FXR +/+ - Control FXR +/+ + RSG FXR -/- - Control FXR -/- + RSG C FXR +/+ + RSG FXR -/- + RSG 250 µm 250 µm

Abdelkarim M et al .. Figure 1

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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. - PowerPoint PPT Presentation

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Page 1: Abdelkarim M et  al .. Figure 1

Abdelkarim M et al.. Figure 1

B

A Weight of BAT

We

igh

t (g

)

FXR+/+ FXR -/-0

0.1

0.2

0.3

0.4

0.5

0.6** ***

0.7Control

RSG

Adipocyte diameter (µm)

Ad

ipo

cy

te f

rac

tio

n (

%)

0

5

10

15

20

0-20 20-40 40-6060-8080-100100-120120-140 140-160 160-180 180-200

0

5

10

15

20

Ad

ipo

cy

te f

rac

tio

n (

%)

FXR+/+ - ControlFXR+/+ + RSG

FXR-/- - ControlFXR-/- + RSG

C FXR+/+ + RSG FXR -/- + RSG

250 µm 250 µm

Page 2: Abdelkarim M et  al .. Figure 1

Abdelkarim M et al.. Figure 2

012345678

CD36 LPL

0

1

2

3

4

5aP2

0

1

2

3

4

0

1

2

3

4

5

6C/EBPβ

0

1

2

3

4

5

6C/EBPα

0

1

2PPARγ

0

1

2

3

4PERILIPIN

0

1

2

3

4ADRP

012345678

FSP27

Adiponectin

0

1

2

3

4

5

0

1

2

3

4S3-12

ControlRSG

ControlRSG

ControlRSG

FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/-

mR

NA

/Cy

clo

ph

ilin

mR

NA

/Cy

clo

ph

ilin

mR

NA

/Cy

clo

ph

ilin

FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/-

FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/- FXR+/+ FXR-/-

***

* **** *** ***

*

*

****

**** ***

C

A

B

Page 3: Abdelkarim M et  al .. Figure 1

Abdelkarim M et al.. Figure 3

mR

NA

/C

yc

lop

hil

in

0

C/EBPα

20

40

60

80

100

120

*

*

*

*

C/EBPβ

0

1

2

3

4

5

6

7

8FXR+/+

FXR-/-FXR+/+

FXR-/-

RSG

Days of Differentiation

mR

NA

/C

yc

lop

hil

in

0

10

20

30

40

50

**

*

*

PPARγFXR+/+

FXR-/-1000

1200aP2

0

200

400

600

800

**

**FXR+/+

FXR-/-

RSG + +- -D4 D8

+ +- -D4 D8

+ +- -D4 D8

+ +- -D4 D8

Page 4: Abdelkarim M et  al .. Figure 1

Abdelkarim M et al.. Figure 4

0

50

100

150

200250

300

350

D0 D2 D4 D8

*

*S3-12

*

0

1000

2000

3000

4000

5000

D0 D2 D4 D8

PERILIPIN

mR

NA

/Cy

clo

ph

ilin

FSP27

0

5000

10000

15000

20000

25000

30000

D0 D2 D4 D8

**

mR

NA

/Cy

clo

ph

ilin

02468

10121416

D0 D2 D4 D8*

*ADRP

Days of differentiation Days of differentiation

FXR+/+

FXR-/-

FXR+/+

FXR-/-FXR+/+

FXR-/-

FXR+/+

FXR-/-

C

µg

gly

ce

rol /

mg

pro

tein

Lipolysis

10

20

30

40

50

60

70

80

D4 D4+ISO D8 D8+ISO

***

**

Days of differentiation

FXR+/+

FXR-/-

mg

TG

/ m

g p

rote

in

10

12

14

16

18

D4 D8

2

4

6

8

D0

*TG content

Days of differentiation

FXR+/+

FXR-/-

Ace

tate

inco

rpo

rati

on

(d

pm

x1

04 ) /

mg

pro

tein

*

D0 D4 D8

5

10

15

20

25

30

**

de novo lipogenesis

Days of differentiation

FXR+/+

FXR-/-

Range of area

Cu

mu

late

d a

rea

(µm

2)

Size distribution of lipid droplets

0

1000

2000

3000

4000

5000

6000

<3 µm2

3-6 µm2

6-18 µm2

18-80 µm

2

>80 µm2

**

*

**FXR+/+

FXR-/-

B

0

50

100

150

200250

300

350

D0 D2 D4 D8

*

*S3-12

*

D0 D2 D4 D8m

RN

A/C

yc

lop

hili

nFSP27

0

5000

10000

15000

20000

25000

30000

D0 D2 D4 D8

**

mR

NA

/Cy

clo

ph

ilin

02468

02468

D0 D2 D4 D8*

*+/+

-/-

+/+

-/-

FXR+/+

FXR-/-

+/+

-/-FXR+/+

FXR-/-

+/+

-/-

FXR+/+

-/-

+/+

-/-

C

µg

gly

ce

rol /

mg

pro

tein

10

20

30

40

50

60

70

80 FXR+/+

FXR-/-

+/+

-/-

+/+

-/-

+/+

-/-

Ace

tate

inco

rpo

rati

on

(d

pm

x1

04 ) /

mg

pro

tein

*

D0 D4 D8

5

10

15

20

25

30

**

de novo lipogenesisFXR+/+

FXR-/-

Ace

tate

inco

rpo

rati

on

(d

pm

x1

04 ) /

mg

pro

tein

*

D0 D4 D8

5

10

15

20

25

30

**

FXR+/+

FXR-/-FXR+/+

FXR-/-

Cu

mu

late

d a

rea

(µm

2)

1000

µ2

-

2

µ2

2

+/+

-/-

B

A

Page 5: Abdelkarim M et  al .. Figure 1

Abdelkarim M et al.. Figure 5

Days of differentiation

B C

mR

NA

/Cyc

lop

hil

in

Days of differentiation

ADRP

0

5

10

15

20

25

30

D0 D4 D80

100

200

300

400

500

600

D0 D4 D8

*

PERILIPIN

FSP27

0

200

400

600

800

1000

D0 D4 D8

*

*

S3-12

D0 D4 D8

mR

NA

/Cyc

lop

hil

in

0

50

100

150

200FXR+/+

FXR -/-

FXR+/+

FXR -/-FXR+/+

FXR -/-

FXR+/+

FXR -/-

AaP2

D0 D4 D8 D0 D4 D8D0 D4 D8D0 D4 D8

mR

NA

/Cyc

lop

hil

in

0100200300400500600700800900

**

0

40

80

120

160

200

*

C/EBP

0

1

2

3

4

5

6

*

***

C/EBP

0

2

4

6

8

10

* *

PPAR

FXR+/+

FXR -/-FXR+/+

FXR -/-FXR+/+

FXR -/-FXR+/+

FXR -/-

aP2

D0 D4 D8 D0 D4 D8D0 D4 D8D0 D4 D8

mR

NA

/Cyc

lop

hil

in

0100200300400500600700800900

**

0

40

80

120

160

200

*

C/EBP

0

1

2

3

4

5

6

*

***

C/EBP

0

2

4

6

8

10

* *

PPARFXR+/+

FXR -/-FXR+/+

FXR -/-FXR+/+

FXR -/-FXR+/+

FXR -/-

FXR+/+

FXR -/-

Day 8Day 0

Days of differentiation

FXR+/+

FXR -/-

Day 8Day 0

mR

NA

/Cyc

lop

hil

in

ADRP

0

5

10

15

20

25

30

D0 D4 D80

100

200

300

400

500

600

D0 D4 D8

*

PERILIPIN

FSP27

0

200

400

600

800

1000

D0 D4 D8

*

*

S3-12

D0 D4 D8

mR

NA

/Cyc

lop

hil

in

0

50

100

150

200FXR+/+

FXR -/-

FXR+/+

FXR -/-FXR+/+

FXR -/-

FXR+/+

FXR -/-

Page 6: Abdelkarim M et  al .. Figure 1

Abdelkarim M et al.. Figure 6

0102030405060708090

100PPAR

0

200

400

600

800

1000

1200aP20

5

10

15

20

25

30C/EBPα

0

1

2

3

4

5

6

7C/EBPβ

0

5000

10000

15000

20000FSP27

0

5

10

15

20

25

30 S3-1202468

10121416

ADRP

0

20

40

60

80

100

120

140PERILIPIN

A BFXR-/- MEFs + empty retrovirus

FXR-/- MEFs + FXR retrovirus

Day 8Days of differentiation Days of differentiation

D0 D2 D4 D8 D0 D2 D4 D8

D0 D2 D4 D8 D0 D2 D4 D8Days of differentiation Days of differentiation

C

mR

NA

/Cy

clo

ph

ilin

mR

NA

/Cy

clo

ph

ilin

mR

NA

/Cy

clo

ph

ilin

mR

NA

/Cy

clo

ph

ilin

FXR-/- +empty retrovirusFXR-/- +FXR retrovirus

FXR+/+ +empty retrovirus

FXR-/- +empty retrovirusFXR-/- +FXR retrovirus

FXR+/+ +empty retrovirus

**

****

***

**

*

*

****

**

*

******

** ***

******

****

**

Page 7: Abdelkarim M et  al .. Figure 1

Abdelkarim M et al.. Figure 7Abdelkarim M et al.. Figure 7

C

D0 D2 D4 D8

Days of differentiation

D0 D2 D4 D8

FXR+/+ FXR -/-

c.i. acidred

Days of differentiation

D0 D2 D4 D8D0 D2 D4 D8

FXR+/+ FXR -/-

-catenin protein

-catenin

c.i. acidred

mR

NA

/Cyc

lop

hil

in

Cyclin

0

1

2

3

*

0

1

2

3

4

5c-Myc

*

mR

NA

/Cyc

lop

hil

in

0

1

2

3

Days of differentiation

0

1

2

3

4

5

*

D

mR

NA

/Cyc

lop

hil

in

LRP5

0

1

2

3

4

5

6

7

8

D0D1D2 D4 D8

* ***

Axin2

0

1

2

3

4

5

6

**

D1D2 D4 D8D0

mR

NA

/Cyc

lop

hil

in

0

1

2

3

4

5

6

7

8

D4 D80

1

2

3

4

5

6

D1D2 D4 D8D0

0

1

2

3

4

5

6

D0 D2 D4 D8D1

*sFRP5

0

1

2

3

4

5

6

D0 D2 D4 D8D1

*

mR

NA

/Cyc

lop

hil

in

sFRP1

0

5

10

15

20

D0 D2 D4 D8D1

*

mR

NA

/Cyc

lop

hil

in

0

5

10

15

20

D0 D2 D4 D8D1

* FXR+/+

FXR-/-FXR+/+

FXR-/-FXR+/+

FXR-/-

D0 D1D2 D4 D8 D0 D1 D2 D4 D8

mR

NA

/Cy

clo

ph

ilin

mR

NA

/Cy

clo

ph

ilin

β-catenin

mR

NA

/Cy

clo

ph

ilin

A B

*

0

1

2

3

4

FXR+/+ FXR-/-

LRP5

Axin2Cyclin D1

c-Myc

0

1

2

3

4

5

FXR+/+ FXR-/-

*

0

1

2

3

4

FXR+/+ FXR-/-

***

0

1

2

3

4

***

FXR+/+ FXR-/- 0

1

2

3

4

**

FXR+/+ FXR-/-

FXR+/+

FXR-/-FXR+/+

FXR-/-FXR+/+

FXR-/-

FXR +/+ -/- -/- +/+ -/- -/- +/+ -/- -/-

+ + - + + - + + -Empty retrovirus

FXRretrovirus

- - +- - +- - +

0

1

2

3

4c-Myc Axin2 LRP5

* **

* ** *

E

FXR +/+ -/- -/-

Empty retrovirus

FXRretrovirus

+ + -

- - +

c.i. acidred

-catenin

c.i. acidred

mR

NA

/Cyc

lop

hil

inm

RN

A/C

yclo

ph

ilin

Page 8: Abdelkarim M et  al .. Figure 1

Abdelkarim M et al.. Figure 8

D0 D4

FXR

sFRP1

Days of differentiation

c.i. acidred

- catenin

c.i. red

+/+ +/+

+-

-/- -/- -/-

- - -

A B

0

0.5

1

1.5

2

2.5

3

3.5

4

FXR +/+ -/- -/- +/+ -/- -/-

sFRP1 - - + - - +

PPAR aP2

***

**