Summary of Study ST003743

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002329. The data can be accessed directly via it's Project DOI: 10.21228/M8KJ93 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST003743
Study Title	Cardiac metabolome signatures of hepato-cardiac FGF21 signaling in pressure overload-induced cardiac hypertrophy
Study Summary	This study investigates the early (3 days) mid- (2 weeks) and late (8 weeks) cardiac metabolome changes driven by FGF21 signaling in the context of pressure overload-induced cardiac hypertrophy. Targeted NMR-based metabolomic profiling was performed on cardiac tissue from control mice at 3 days, 2 weeks, and 8 weeks following transverse aortic constriction (TAC), as well as from hepatocyte-specific (HEP-FGF21) and cardiomyocyte specific (CM-FGF21) Fgf21 knockout mice at the 8-week post-TAC timepoint. Sham-operated wild type mice and mice expressing Cre in hepatocytes or cardiomyocytes served as controls for each timepoint. The early and mid-timepoints were selected to capture transient and potentially triggering metabolic adaptations that precede overt cardiac remodeling, while the late timepoint allowed assessment of established metabolic reprogramming in advanced hypertrophy. Inclusion of the knockout models at 8 weeks enabled dissection of the respective contributions of endocrine (hepatocyte-derived) and autocrine (cardiomyocyte-derived) FGF21 signaling to the cardiac metabolome phenotype. The analysis revealed time-dependent alterations in the metabolic profile, with lower glucose and glucose derived metabolites in early timepoints and accumulation of Branched-Chain Amino Acids when pathological hypertrophy has fully developed (8 weeks). Ablation of Fgf21 in either the hepatocytes or cardiomyocytes mitigated maladaptive metabolic remodeling at 8 weeks, highlighting distinct and cooperative roles of hepatic and cardiac FGF21 in the progression of hypertrophy.
Institute	University of Cincinnati College of Medicine
Last Name	Siokatas
First Name	Georgios
Address	231 ALBERT SABIN WAY, University of Cincinnati, Cincinnati, OH, 45267-2827
Email	siokatgs@ucmail.uc.edu
Phone	5133028282
Submit Date	2025-02-19
Raw Data Available	Yes
Raw Data File Type(s)	fid, 1r
Analysis Type Detail	NMR
Release Date	2025-03-04
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR002329
Project DOI:	doi: 10.21228/M8KJ93
Project Title:	Hepato-cardiac interorgan communication controls cardiac hypertrophy via combined endocrine-autocrine FGF21 signaling.
Project Summary:	Fibroblast Growth Factor (FGF) 21 is a hormone produced mainly by the liver but also other organs, including the heart. Although FGF21 analogs are used for treating obesity and metabolic syndrome in humans, preclinical and clinical studies have elicited mixed results about whether prolonged FGF21 signaling is protective or detrimental for cardiac function. Based on our findings, showing elevated serum and cardiac FGF21 levels in humans with increased left ventricular afterload, we explored involvement of FGF21 in cardiac hypertrophy. Our mouse studies revealed an interorgan liver-heart crosstalk mechanism which is controlled by initial hepatic FGF21 release followed by induction of cardiomyocyte FGF21 expression. Tissue-specific genetic ablation or anti-sense oligonucleotides-based inhibition of FGF21 showed that in response to pressure overload, cardiomyocyte FGF21 upregulation is a critical event that is stimulated by liver-derived FGF21 and drives cardiac hypertrophy likely by interfering with cardioprotective oxytocin signaling. Conclusively, a hepato-cardiac FGF21-based signaling axis governs cardiac hypertrophy.
Institute:	University of Cincinnati College of Medicine
Last Name:	Siokatas
First Name:	Georgios
Address:	231 ALBERT SABIN WAY, University of Cincinnati, Cincinnati, OH, 45267-2827
Email:	siokatgs@ucmail.uc.edu
Phone:	5133028282

Subject:

Subject ID:	SU003875
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Genotype	Timepoint
SA408142	FGF-H40	Alb-Cre Fgf21-/-	8 Weeks
SA408143	FGF-H39	Alb-Cre Fgf21-/-	8 Weeks
SA408144	FGF-H38	Alb-Cre Fgf21-/-	8 Weeks
SA408145	FGF-H37	Alb-Cre Fgf21-/-	8 Weeks
SA408146	FGF-H36	Alb-Cre Fgf21-/-	8 Weeks
SA408147	FGF-H14	Fgf21 fl/fl	2 Weeks
SA408148	FGF-H17	Fgf21 fl/fl	2 Weeks
SA408149	FGF-H16	Fgf21 fl/fl	2 Weeks
SA408150	FGF-H15	Fgf21 fl/fl	2 Weeks
SA408151	FGF-H20	Fgf21 fl/fl	2 Weeks
SA408152	FGF-H13	Fgf21 fl/fl	2 Weeks
SA408153	FGF-H12	Fgf21 fl/fl	2 Weeks
SA408154	FGF-H11	Fgf21 fl/fl	2 Weeks
SA408155	FGF-H19	Fgf21 fl/fl	2 Weeks
SA408156	FGF-H18	Fgf21 fl/fl	2 Weeks
SA408157	FGF-H02	Fgf21 fl/fl	3 Days
SA408158	FGF-H01	Fgf21 fl/fl	3 Days
SA408159	FGF-H10	Fgf21 fl/fl	3 Days
SA408160	FGF-H04	Fgf21 fl/fl	3 Days
SA408161	FGF-H05	Fgf21 fl/fl	3 Days
SA408162	FGF-H06	Fgf21 fl/fl	3 Days
SA408163	FGF-H07	Fgf21 fl/fl	3 Days
SA408164	FGF-H08	Fgf21 fl/fl	3 Days
SA408165	FGF-H09	Fgf21 fl/fl	3 Days
SA408166	FGF-H30	Fgf21 fl/fl	8 Weeks
SA408167	FGF-H21	Fgf21 fl/fl	8 Weeks
SA408168	FGF-H29	Fgf21 fl/fl	8 Weeks
SA408169	FGF-H28	Fgf21 fl/fl	8 Weeks
SA408170	FGF-H27	Fgf21 fl/fl	8 Weeks
SA408171	FGF-H26	Fgf21 fl/fl	8 Weeks
SA408172	FGF-H25	Fgf21 fl/fl	8 Weeks
SA408173	FGF-H24	Fgf21 fl/fl	8 Weeks
SA408174	FGF-H23	Fgf21 fl/fl	8 Weeks
SA408175	FGF-H22	Fgf21 fl/fl	8 Weeks
SA408141	FGF-H03	-	Fgf21 fl/fl
SA408176	FGF-H32	αMHC-Cre Fgf21-/-	8 Weeks
SA408177	FGF-H33	αMHC-Cre Fgf21-/-	8 Weeks
SA408178	FGF-H34	αMHC-Cre Fgf21-/-	8 Weeks
SA408179	FGF-H35	αMHC-Cre Fgf21-/-	8 Weeks
SA408180	FGF-H31	αMHC-Cre Fgf21-/-	8 Weeks

Showing results 1 to 40 of 40

Showing results 1 to 40 of 40

Collection:

Collection ID:	CO003868
Collection Summary:	Collection and Storage: Hearts were perfused with ice-cold PBS, carefully dissected, and snap-frozen in liquid nitrogen. All samples were stored at -80°C until further processing.
Sample Type:	Heart

Treatment:

Treatment ID:	TR003884
Treatment Summary:	Mice underwent Sham or TAC (Transverse Aortic Constriction) surgery. A thoracotomy was performed, and the transverse aorta was isolated and tied around 27-gauge needle, which was removed to generate the desired constriction. The incision to the rib cage was closed using a 6.0 silk suture (AD Surgical) and the skin wound was closed with a 5.0 silk suture. (AD Surgical). The sham procedure was identical except that aortic arch was not constricted. Tissues were collected 3 days, 2 weeks or 8 weeks post-surgery.

Treatment ID:

TR003884

Treatment Summary:

Mice underwent Sham or TAC (Transverse Aortic Constriction) surgery. A thoracotomy was performed, and the transverse aorta was isolated and tied around 27-gauge needle, which was removed to generate the desired constriction. The incision to the rib cage was closed using a 6.0 silk suture (AD Surgical) and the skin wound was closed with a 5.0 silk suture. (AD Surgical). The sham procedure was identical except that aortic arch was not constricted. Tissues were collected 3 days, 2 weeks or 8 weeks post-surgery.

Sample Preparation:

Sampleprep ID:	SP003881
Sampleprep Summary:	Each individual sample was homogenized using a cryogenic ball-mill homogenizer (Cryomill, Retsch Inc.) and weighted into bead tubes (2.8 mm, MO BIO, catalog #13114-50) for extraction. Based on the weights of tissues, the solvent volumes used for extraction were calculated for each sample. Modified Bligh and Dyer extraction1-3 was used to obtain polar metabolites. Briefly, cold methanol and water were added to the samples in bead tubes and homogenized for 30 s. The samples were transferred into glass tubes containing cold chloroform and water. The final methanol:chloroform:water ratio is 2:2:1.8. The mixture was vortexed, incubated on ice for 10 min, then centrifuged at 2000x gn for 5 min. The polar phase was transferred into 1.5mL Eppendorf tube and dried by vacuum centrifuge for 4-5 hrs at room temperature. The dried metabolites were resuspended in 220 uL of NMR buffer containing 100mM phosphate buffer, pH7.3, 1mM TMSP (3-Trimethylsilyl 2,2,3,3-d4 propinoate), 1mg/mL sodium azide) prepared in D2O. Final volume of 200 uL of each sample was transferred into 3 mm NMR tube (Bruker) for data collection

Sampleprep ID:

SP003881

Sampleprep Summary:

Each individual sample was homogenized using a cryogenic ball-mill homogenizer (Cryomill, Retsch Inc.) and weighted into bead tubes (2.8 mm, MO BIO, catalog #13114-50) for extraction. Based on the weights of tissues, the solvent volumes used for extraction were calculated for each sample. Modified Bligh and Dyer extraction1-3 was used to obtain polar metabolites. Briefly, cold methanol and water were added to the samples in bead tubes and homogenized for 30 s. The samples were transferred into glass tubes containing cold chloroform and water. The final methanol:chloroform:water ratio is 2:2:1.8. The mixture was vortexed, incubated on ice for 10 min, then centrifuged at 2000x gn for 5 min. The polar phase was transferred into 1.5mL Eppendorf tube and dried by vacuum centrifuge for 4-5 hrs at room temperature. The dried metabolites were resuspended in 220 uL of NMR buffer containing 100mM phosphate buffer, pH7.3, 1mM TMSP (3-Trimethylsilyl 2,2,3,3-d4 propinoate), 1mg/mL sodium azide) prepared in D2O. Final volume of 200 uL of each sample was transferred into 3 mm NMR tube (Bruker) for data collection

Analysis:

Analysis ID:	AN006147
Analysis Type:	NMR
Num Factors:	6
Num Metabolites:	49
Units:	mM

NMR:

NMR ID:	NM000308
Analysis ID:	AN006147
Instrument Name:	Bruker Avance III
Instrument Type:	FT-NMR
NMR Experiment Type:	1D-1H
Field Frequency Lock:	Detuterium
Standard Concentration:	1 mM
Spectrometer Frequency:	600 MHz
NMR Probe:	Prodigy 5mm BBI
NMR Solvent:	D2O
NMR Tube Size:	103.5 mm x 5 mm
Shimming Method:	Topshim
Pulse Sequence:	noesygppr1d