KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit polyclonal anti-UCP1 antibody	Abcam	Cat# ab10983; RRID:AB_2241462
Rabbit polyclonal anti-DIO2 antibody	Abcam	Cat# ab135711; RRID:AB_2892107
Polyclonal goat anti-FGF21	R&D	Cat# AF3057; RRID:AB_2104611
Rabbit polyclonal anti-phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)	Cell Signaling	Cat# 9101; RRID:AB_331646
Anti-p44/42 MAPK (Erk1/2) (137F5) rabbit mAb	Cell Signaling	Cat# 4695; RRID:AB_390779
Rabbit anti-phospho-PLCγ1 (Tyr783) antibody	Cell Signaling	Cat# 2821; RRID:AB_330855
Rabbit anti-PLCγ1 (D9H10) XP Rabbit mAb	Cell Signaling	Cat# 5690; RRID:AB_10691383
Chemicals, peptides, and recombinant proteins
CL 316,243 hydrate	Sigma-Aldrich	Cat# C5976
SB-203,580	Sigma-Aldrich	Cat# S8307
H 89 dihydrochloride	TOCRIS	Cat# 2910
PD98059	Selleck Chemicals	Cat# S1177
PD173074	Sigma-Aldrich	Cat# P2499
PD 0325901	Sigma-Aldrich	Cat# PZ0162
U-73122	Sigma-Aldrich	Cat# U6756
BAPTA-AM	ThermoFisher	Cat# B1205
ATGL Inhibitor, Atglistatin	Sigma-Aldrich	Cat# 5.30151
Recombinant mouse FGF21 Protein	R&D Systems	Cat# 8409-FG-025/CF
Critical commercial assays
NEFA kit	WAKO	Cat# 999–34691, 995–34791, 993–35191, 276–76491
FGF21 Quantikine ELISA	R&D	Cat# MF2100
Mouse IL-6 Quantikine ELISA Kit	R&D	Cat# SM6000B
cAMP Enzyme Immunoassay Kit	Sigma-Aldrich	Cat# CA201
Deposited data
RNA-Sequencing analysis of WT and FGF21-KO PPDIVs treated with or without CL-316,243	This paper	SRA: PRJNA725497
Experimental models: Cell lines
3T3-L1 preadipocytes	ATCC	CL-173
Primary preadipocytes	C57Bl6 iWAT	NA
Mouse primary hepatocyte	C57Bl6 liver	NA
Experimental models: Organisms/strains
Mouse: whole body FGF21-KO	Potthoff et al., 2009	NA
Mouse: liver-specific FGF21-KO (LFKO)	Markan et al., 2014	NA
Mouse: adipose-specific β-Klotho-KO (ABKO)	Lan et al., 2017	NA
Mouse: adipose-specific FGF21 Tg	This paper	NA
Oligonucleotides
25 nmole DNA Oligo, Standard Desalting (primers sequences are listed in Table S1)	IDT	N/A
Software and algorithms
Prism 6.0	GraphPad	6.0