Lean Obese A. B Class Changes Untreated + Gem/Pac Untreated + Gem/Pac

Lean Animals 500000 L4 400000 L3 L2 300000 200000 100000 Relative Abundance Relative 0 Bacilli Clostridia Bacteroidia Actinobacteria errucomicrobiae V Gammaproteobacteria

Obese Animals O4 800000 O3 O2 O1 600000

400000

200000 Relative Abundance Relative 0 Bacilli Clostridia Bacteroidia Actinobacteria errucomicrobiae V Gammaproteobacteria

A. B. C.

40 * 4 400 Day1 * * Day 30 ) 30 l 300

) 3

s m L g/ m / a l ide s r r g 20 2 e 200 c ol ( u r y ht ( mm o g ig l i r e T 100

W 10 1 ho le st e C

0 0 0 Adjusted Control High Fat (Lean) Diet (Obesogenic) Diet

Lean Mice Lean Mice Obese Mice Obese Mice

Tumor Take D. 250 E. * 100 r ) o

L 200 m

u 80 t g/ d 150 e ( m

s 60 o 100 lu c mals w ith

G 40

50 f an i o 20 Bloo d % 0 0 Adjusted Control High Fat (Lean) Diet (Obesogenic) Diet Lean Mice Obese Mice

High Fat Diet F. Tumor progression G. Adjusted Control Diet 4000 * ) 3000

2000 olume (mm

1000 umor v T

0 0 10 20 30 Days after tumor implantation

Adjusted Control H&E staining of representative tumors High Fat Diet A. B. MIA-PaCa2 S2VP10

4 4

* * 3 3

2 2 Absorbance Absorbance 1 1 (function of cell growth ) (function of cell growth ) 0 0 20 40 60 0 0 20 40 60 Time in hours Time in hours

Control Pre Q1 100nM

Fold change over Fold change over control

control 0.0 0.5 1.0 1.5 2.0 2.5 Fold change in mRNA expression (Normalized to Control) 0 1 2 3 4

0.0 0.5 1.0 1.5 AKR1C2 BAG2 SiPRDX1 e ciency APOE FHL2

ATOX1 GCLM Pathway CAT GLA CCL5 HMOX1 CYGB HSP90AA1 DHCR24 LHPP

DUOX1 Activity DUOX2 NCOA7 DUSP1 NQO1 EPX PTGR1 FOXM1 SLC7A11 FTH1 SPINK1 GCLC TRAPPC6A GCLM

Oxidative stressresponse TXN GPX1 GPX2 TXNRD1

20nM siPRDX1 10nM siPRDX1 N GPX3

S GPX4 GPX5 GSR GSS HMOX1 HSPA1A KRT LPO MBL2 Fold change over MPO MSRA control 0.0 0.5 1.0 1.5 2.0 NQ01 10 12 14 16 18 20 NUDT1 PDLIM1 SOD1 Viability PRDX2 SOD2 Normalized to untreated PRDX5 SOD3 0.0 0.5 1.0 1.5 PRDX6 ALOX12 PRNP CCS R RNF7 DUOX1 O S Control SELENEP DUOX2

SELENOS MT3 metabolis SIRT2 NCF1 SOD1 NCF2 SOD2

siPrdx1 NOS2 (iNOS) SQSTM1 NOX4 PreQ 50nM

Control SRXN1 NOX5 TPO UCP2 m TTN AOX1 TXNRD1 BNIP3 TXNRd2 EPHX2 TXN MPV17 SFTPD A. B. CD133/Perilipin 6 LF s 1.5

HF * 4

pi n+ even t 1.0 il i /Pe r ng/m l

Cytokine s 2 0.5 f CD133 + o

0 io 0.0 Ra t IL6 Lean Obese IL22 IFN γ TNF α IL17F IL17A

C. D. ACM CD133 Flow Adipocyte conditioned media 1.5 3 t 1.0 2 eve n

0.5 1 f CD133 + o Cytokines (ng/ml ) %

0.0 0

Control ACM IL6 IL22 IFN γ TNF α IL17F IL17A

E.

4 CSC PCR array after treatment with Pre-Q

3

2 contro l

1 Fold change ove r

0 T AZ IL8 TM KIT T AXL AP1 A EGF ENG MYC SMO BMI1 JAK2 KLF4 DLL4 PL A Y JAG1 ZEB1 ZEB2 TXN1 CD24 CD34 CD38 CD44 THY1 SOX2 BMP7 DDR1 NOS2 MUC1 WNT1 WEE1 ITGA2 KITLG SNAI1 MYCN S TA T3 FLOT2 A WWC1 NFKB1 ABCB5 FGFR2 ERBB2 FOXA2 FOXP1 PTCH1 GSK3B LIN28B PLAUR ABCG2 DACH1 HDAC1 ALCAM EPCAM PROM1 NANOG POU5F1 TGFBR1 NOTCH1 NOTCH2 PECAM1 ALDH1A1