REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
GDF15 (G-5)	Santa Cruz	Cat# sc-377195
GADD 153 (B-3)	Santa Cruz	Cat# sc-7351; RRID: AB_627411
Phospho S51 EIF2a	Epitomics/Abcam	Cat# ab32157; RRID: AB_732117
ATF4	Dr David Ron (CIMR)	(Harding et al., 2000a)
Calnexin	Abcam	Cat# ab75801; RRID: AB_1310022
Anti-rabbit IgG, HRP-linked Antibody	Cell Signaling Technologies	Cat# 7074; RRID: AB_2099233
Anti-mouse IgG, HRP-linked Antibody	Cell Signaling Technologies	Cat# 7076; RRID: AB_330924
Biological Samples
C57BL/6J mice tissues	Charles River	JAX C57BL/6J; RRID: IMSR_JAX:000664
C57BL/6J mice tissues	In house (University of Cambridge)	N/A; RRID: IMSR_JAX:000664
Human samples (Blood)	Various	See Method Details for details
Chemicals, Peptides, and Recombinant Proteins
Recombinant Human GDF15	Peprotech	Cat# 120-28
Lithium Chloride	Sigma	Cat# LX0331
Tunicamycin	Sigma	Cat# T7765
Thapsigargin	Sigma	Cat# T9033
Cobalt(II) chloride hexahydrate	Sigma	Cat# C8661
L-Histidinol dihydrochloride	Sigma	Cat# H6647
ISRIB	Sigma	Cat# SML0843
PERKi - GSK2606414	Calbiochem	Cat# 516535
TRI Reagent (Triazol)	Sigma	Cat# T9424
Chloroform	Honeywell	Cat# C2432
Ethanol, puriss. p.a., absolute, ≥ 99.8% (GC)	Sigma	Cat# 32221-M
DMEM	Sigma	Cat# D6546
D-PBS	Sigma	Cat# D8537
Hanks’ Balanced Salt Solution	Sigma	Cat# H9269
L-Glutamine	Sigma	Cat# G7513
Penicillin-Streptomycin	Sigma	Cat# P0781
MEM Non-essential Amino Acid	Sigma	Cat# M7145
Sodium pyruvate	Sigma	Cat# S8636
2-Mercaptoethanol	GIBCO	Cat# 31350-010
FBS	GIBCO	Cat# 10270-106
FetalClone II Serum	Hyclone	Cat# SH30066.03
Sybr Green MasterMix	Applied Biosystems	Cat# 4309155
Taqman MasterMix	Applied Biosystems	Cat# 4304437
cOmplete, Mini Protease Inhibitor Cocktail	Sigma	Cat# 11836153001
PhosSTOP	Sigma	Cat# 4906845001
Random primers	Promega	Cat# C1181
RNasin Plus Ribonuclease inhibitor	Promega	Cat# N2611
MMLV Reverse Transcriptase	Promega	Cat# M1701
DNase1	QIAGEN	Cat# 79254
DNase1	Thermofisher Scientific	Cat# 18068015
Lipofectamine RNAiMAX	Invitrogen	Cat# 13778-150
Collagenase Type II from Clostridium histolyticum	Sigma	Cat# C6885
NuPAGE 4-12% Bis-Tris Protein Gels, 1.5 mm, 10-well	Novex	Cat# NP0335BOX
NuPAGE MOPS SDS Running Buffer (20X)	Novex	Cat# NP0001
NuPAGE LDS Sample Buffer (4X)	Novex	Cat# NP0007
iBlot Transfer Stack, nitrocellulose, regular size	Invitrogen	Cat# IB301001
Dual Color Standards	BIO-RAD	Cat# 1610374
Bovine Serum Albumin	Sigma	Cat# A7906
Immobilon Western (Chemiluminescent HRP Substrate)	Millipore	Cat# WBKLS0500
ECL Western Blotting Detection Reagents	GE Healthcare	Cat# RPN2106
Dolethal 200mg/mL Solution for injection	Vetoquinol UK Ltd	N/A
Critical Commercial Assays
RNAeasy Mini Kit	QIAGEN	Cat# 74106
Qiashredder	QIAGEN	Cat# 79656
Human total GLP-1	Meso Scale Discovery	Cat# K150JVC-1
Human Active GLP-1	R&D Systems	Cat# DY957
Human Insulin	Diasorin	Cat# 310360
Human GDF15 Elisa	R&D Systems	Cat# DY957
Human FGF21 Elisa	R&D Systems	Cat# DF2100
Human Leptin Elisa	In-house platform system using R&D Leptin: Cat # MAB398, BAM398 and 398-LP	https://www.cuh.nhs.uk/core-biochemical-assay-laboratory
Mouse GDF15 Elisa	R&D Systems	Cat# DY6385
Mouse FGF21 Elisa	R&D Systems	Cat# MF2100
Mouse Leptin/insulin 2-Plex	Meso Scale Discovery	Cat# K15124C
Experimental Models: Cell Lines
Mouse Embryonic Fibroblasts (MEFs)	Dr David Ron (CIMR)	(Scheuner et al., 2001, Harding et al., 2003)
HeLa	ATCC	Cat# CCL-2; RRID: CVCL_0030
HuH7	Dr Albert Pol, IDIBAPS, Barcelona	Cat# JCRB0403; RRID: CVCL_0336
A549	ATCC	Cat# CCL-185; RRID: CVCL_0023
3T3-L1	Zenbio	Cat# SP-L1-F
Experimental Models: Organisms/Strains
M. musculus: C57BL/6J mice strain	Charles River	JAX C57BL/6J; RRID: IMSR_JAX:000664
M. musculus: C57BL/6J mice strain	In House (University of Cambridge)	N/A; RRID: IMSR_JAX:000664
M. musculus: C57BL/6N mice strain	Taconic	C57BL/6NTac; RRID: MGI:5658006
Oligonucleotides
Control siRNA	Dharmacon	Cat# D-001810-10-20
DDIT3 siRNA smartpool On-target Plus	Dharmacon	Cat# L-062068-00-0005
Human GDF15 Taqman assay	Thermo Fisher Scientific	Cat# Hs00171132_m1
Human FGF21 Taqman assay	Thermo Fisher Scientific	Cat# Hs00173927_m1
Mouse GDF15 Taqman assay	Thermo Fisher Scientific	Cat# Mm00442228_m1
Mouse FGF21 Taqman assay	Thermo Fisher Scientific	Cat# Mm00840165_g1
Human GAPDH Taqman assay	Thermo Fisher Scientific	Cat# Hs02758991_g1
Human HPRT Taqman assay	Thermo Fisher Scientific	Cat# Hs02800695_m1
Mouse HPRT Forward (AGCCTAAGATGAGCGCAAGT); Mouse HPRT Reverse (GGCCACAGGACTAGAACACC)	This paper	N/A
Mouse B2M Forward (ACTGATACATACGCCTGCAGAGTT); Mouse B2M Reverse (TCACATGTCTCGATCCCAGTAGA)	This paper	N/A
Mouse 36b4 Forward (AGATGCAGCAGATCCGCAT); Mouse 36b4 Reverse (GTTCTTGCCCATCAGCACC)	This paper	N/A
Mouse F4/80 Forward CAGATACAGCAATGCCAAGCA; Mouse F4/80 Reverse GATTGTGAAGGTAGCATTCACAAGTG; Mouse F4/80 Probe FAM- GCAGGGCAGGGATCTTGGTTATGC-TAMRA	This paper	N/A
Mouse CHOP Forward (CCACCACACCTGAAAGCAGAA); Mouse CHOP Reverse (AGGTGAAAGGCAGGGACTCA)	This paper	(Oslowski and Urano, 2011)
Mouse ATF4 Forward (GGGTTCTGTCTTCCACTCCA); Mouse ATF4 Reverse (AAGCAGCAGAGTCAGGCTTTC)	This paper	(Oslowski and Urano, 2011)
Software and Algorithms
GraphPad PRISM 7	1992-2017 GraphPad Software	RRID: SCR_000306
Illustrator (CS6)	Adobe	RRID: SCR_010279
Photoshop (CS6)	Adobe	RRID: SCR_014199
Other
Chow diet (mouse studies)	Safe Diets	Cat# R105-25
Chow diet (mouse studies)	Purina (Lab Diet)	Cat# 5053
45% High Fat Diet (mouse studies)	Research Diets	Cat# D12451i
E Ensure Plus	Abbot Laboratories	N/A
ImageQuant LAS 4000	GE Healthcare	Cat# 28955810
Nanodrop 2000	Thermofisher Scientific	N/A
FastPrep-24	MP Biomedical	Cat# 116004500
AlphaTrack2 Glucometer	Abbot Laboratories	Cat# CFMU305-H0201
AlphaTrack2 strips	Zoetis	Cat# 71681-01
Hematocrit tubes Na-Heparinized	Hawksley	Cat# 01605-00
Microtube 1.1 mL Z Gel	Sarstedt AG & Co	Cat# 41.1378.005
Microtube 1.1 mL Z Gel	Sarstedt AG & Co	Cat# 41.1500.005
Lysing Matrix D, 2 mL Tube	MP Biomedical	Cat# 116913100
Sterile Cell strainer (100 μm nylon mesh)	Fisherbrand	22363549
Minispec LF series (TD-NMR)	Bruker	Cat# LF50
Lunar PIXImus Mouse Densitometer	GE Healthcare Systems	N/A
iBlot Dry Blotting System	Invitrogen	N/A
PowerPac Universal Power Supply	BIO-RAD	Cat# 1645070
XCell SureLock Mini-Cell Electrophoresis System	Invitrogen	Cat# EI0001
QuantStudio 7 Flex Real-Time PCR System	ThermoFisher Scientific	Cat# 4485701