REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
AKT	CST	Cat #4691S
p-AKT	CST	Cat #S473
AMPK	CST	Cat #2532S
p-AMPK	CST	Cat #2535S
MUP1	Abcam	Cat #ab95198
MUP11	Thermo Fisher Scientific	Cat #PIPA5112879
MUP12	Thermo Fisher Scientific	Cat #NB125147
GAPDH	CST	Cat #2118S
p-AKT	CST	Cat #S473
AMPK	CST	Cat #2532S
p-AMPK	CST	Cat #2535S
MUP1	Abcam	Cat #ab95198
MUP11	Thermo Fisher Scientific	Cat #PIPA5112879
MUP12	Thermo Fisher Scientific	Cat #NB125147
GAPDH	CST	Cat #2118S
Chemicals, peptides, and recombinant proteins
High-fat diet (60% kcal from Fat)	Research Diets Inc.	Cat #D12492i
IVISbrite D-Luciferin	Revvity	Cat #770504
Humulin-R	NDC	Cat #0002-8215-17 (HI-213)
Insulin, Cell culture	Roche	Cat #11376497001
Dextrose Anydrous	VWR	Cat #BDH9230
Qiazol	Qiagen	Cat #79306
DMEM Low Glucose	Invitrogen	Cat #11885-084
DMEM High Glucose	Thermo Fisher Scientific	Cat #1960-069
Dexamethasone	Sigma	Cat #D-4902
Fetal Bovine Serum	Corning	Cat #35-010-CV
ITS mix	Sigma	Cat #I3146
Indomethacin	Sigma	Cat #I7378
Linoleic-acid Albumin	Sigma	Cat #L9530
L-Ascorbic Acid Phosphate	Sigma	Cat #A8960
IBMX	Sigma	Cat #I5879
Penicillin/Streptomycin	Gibco	Cat #504284
Trypsin EDTA 0.25%	VWR	Cat #02-0154-0100
PBS	VWR	Cat #E504
Smooth Muscle Cell Growth Medium 2 and its Supplement Mix	Promocell	Cat #C-22062
Pyruvate	Gibco	Cat #11360
Glutamax	Gibco	Cat #35050
L-Proline	Sigma	Cat #D49752
T3	Sigma	Cat #T6397
Rosiglitazone	Sigma	Cat #R2408-10MG
TrypLE Express Enzyme (1X), phenol	Thermo Fisher Scientific	Cat #12605010
Critical commercial assays
Insulin ELISA	Millipore	Cat #EZRMI-13K
Adiponectin ELISA	Sigma	Cat #RAB1115-1KT
FGF21 ELISA	BioVendor R&D	Cat #RD291108200R
Qiagen RNeasy Plus Mini Kit	Qiagen	Cat #74134
Agilent BioAnalyzer RNA Nano Kit	Agilent Technologies	Cat #5067-1511
Invitrogen Qubit RNA HS Assay Kit	Thermo Fisher Scientific	Cat #Q32852
NEBNext Ultra II Directional RNA Library Prep Kit	NEB	Cat #E7760L
NEBNext Poly (A) mRNA Magnetic Isolation Module	NEB	Cat #E7490
Agilent BioAnalyzer HS DNA Kit	Agilent	Cat #5067-4626
Invitrogen Qubit DNA HS Assay Kit	Thermo Fisher Scientific	Cat #Q32854
Deposited data
Bulk RNA-sequencing data (Liver)	Submitted on NCBI GEO database (https://www.ncbi.nlm.nih.gov/geo/)	Accession number: GSE250078
Experimental models: Cell lines
AgeX-NP88 cell line	AgeX Therapeutics	Not Applicable
Experimental models: Organisms/strains
FGF21 Knock-out mice	Jackson Laboratory	B6.129Sv(Cg)-Fgf21tm1.1Djm/
Wild-type mice	Charles River laboratories	C57BL/6J
Luciferase Transgenic mice	Jackson Laboratory	FVB-Tg [CAG-luc,-GFP] L2G85Chco/J
NSG mice	Jackson Laboratory	NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ
Oligonucleotides
Oligonucleotides	This paper: Table S1
Software and algorithms
GraphPad Prism 7	GraphPad Software	https://www.graphpad.com
R version 4.2.2	R Development Core Team, 2011	https://www.r-project.org/
Fastp version 0.20.0	Shifu Chen	Shifu Chen. 2023. Ultrafast one-pass FASTQ data preprocessing, quality control, and deduplication using fastp. iMeta 2: e107. https://doi.org/10.1002/imt2.10778
Kallisto version 0.46.1	Pachter Lab	Nicolas L Bray, Harold Pimentel, Páll Melsted and Lior Pachter, Near-optimal probabilistic RNA-seq quantification, Nature Biotechnology 34, 525–527 (2016), https://doi.org/10.1038/nbt.351979
clusterProfiler version 4.6.0	Guangchuang Yu	Yu G, Wang L, Han Y and He Q∗. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS: A Journal of Integrative Biology. 2012, 16(5):284-28780
Image J	NIH	Rasband, W.S., ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, USA, https://imagej.net/ij/, 1997-2018.81