Summary of Study ST003851

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.

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Study ID	ST003851
Study Title	Lipidomic 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 lipidome changes driven by FGF21 signaling in the context of pressure overload-induced cardiac hypertrophy. Untargeted LC-MS/MS lipidomic profiling was performed on cardiac tissue from 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 at each stage. The early timepoints were chosen to capture transient and potentially initiating cardiac lipidome adaptations prior to overt cardiac remodeling, while the late timepoint provided insight into established lipidome reprogramming associated with advanced hypertrophy. Inclusion of the knockout models at 8 weeks enabled the dissection of endocrine (hepatocyte-derived) versus autocrine (cardiomyocyte-derived) FGF21 contributions to cardiac lipid metabolism. The analysis revealed time-dependent shifts in the cardiac lipidome, with an early increase in triglyceride species observed at 3 days post-TAC, followed by progressive accumulation of phospholipids—including phosphatidylcholines (PC), phosphatidylethanolamines (PE), and phosphatidylserines (PS)at 2 and 8 weeks. Ablation of Fgf21 in either hepatocytes or cardiomyocytes significantly attenuated this phospholipid accumulation at 8 weeks, suggesting that both hepatic and cardiac FGF21 contribute to maladaptive lipidome remodeling during hypertrophic progression.
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	2025-03-27
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2025-05-01
Release Version	1

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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:	SU003985
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	Surgery
SA420866	FGF-H40	Alb-Cre Fgf21-/-	8 Weeks	TAC
SA420867	FGF-H39	Alb-Cre Fgf21-/-	8 Weeks	TAC
SA420868	FGF-H38	Alb-Cre Fgf21-/-	8 Weeks	TAC
SA420869	FGF-H37	Alb-Cre Fgf21-/-	8 Weeks	TAC
SA420870	FGF-H36	Alb-Cre Fgf21-/-	8 Weeks	TAC
SA420871	FGF-H13	Fgf21 fl/fl	2 Weeks	Sham
SA420872	FGF-H15	Fgf21 fl/fl	2 Weeks	Sham
SA420873	FGF-H14	Fgf21 fl/fl	2 Weeks	Sham
SA420874	FGF-H11	Fgf21 fl/fl	2 Weeks	Sham
SA420875	FGF-H12	Fgf21 fl/fl	2 Weeks	Sham
SA420876	FGF-H16	Fgf21 fl/fl	2 Weeks	TAC
SA420877	FGF-H20	Fgf21 fl/fl	2 Weeks	TAC
SA420878	FGF-H19	Fgf21 fl/fl	2 Weeks	TAC
SA420879	FGF-H18	Fgf21 fl/fl	2 Weeks	TAC
SA420880	FGF-H17	Fgf21 fl/fl	2 Weeks	TAC
SA420881	FGF-H02	Fgf21 fl/fl	3 Days	Sham
SA420882	FGF-H01	Fgf21 fl/fl	3 Days	Sham
SA420883	FGF-H03	Fgf21 fl/fl	3 Days	Sham
SA420884	FGF-H04	Fgf21 fl/fl	3 Days	Sham
SA420885	FGF-H05	Fgf21 fl/fl	3 Days	Sham
SA420886	FGF-H10	Fgf21 fl/fl	3 Days	TAC
SA420887	FGF-H09	Fgf21 fl/fl	3 Days	TAC
SA420888	FGF-H08	Fgf21 fl/fl	3 Days	TAC
SA420889	FGF-H06	Fgf21 fl/fl	3 Days	TAC
SA420890	FGF-H07	Fgf21 fl/fl	3 Days	TAC
SA420891	FGF-H21	Fgf21 fl/fl	8 Weeks	Sham
SA420892	FGF-H24	Fgf21 fl/fl	8 Weeks	Sham
SA420893	FGF-H25	Fgf21 fl/fl	8 Weeks	Sham
SA420894	FGF-H23	Fgf21 fl/fl	8 Weeks	Sham
SA420895	FGF-H22	Fgf21 fl/fl	8 Weeks	Sham
SA420896	FGF-H28	Fgf21 fl/fl	8 Weeks	TAC
SA420897	FGF-H29	Fgf21 fl/fl	8 Weeks	TAC
SA420898	FGF-H27	Fgf21 fl/fl	8 Weeks	TAC
SA420899	FGF-H26	Fgf21 fl/fl	8 Weeks	TAC
SA420900	FGF-H30	Fgf21 fl/fl	8 Weeks	TAC
SA420901	FGF-H31	αMHC-Cre Fgf21-/-	8 Weeks	TAC
SA420902	FGF-H32	αMHC-Cre Fgf21-/-	8 Weeks	TAC
SA420903	FGF-H33	αMHC-Cre Fgf21-/-	8 Weeks	TAC
SA420904	FGF-H34	αMHC-Cre Fgf21-/-	8 Weeks	TAC
SA420905	FGF-H35	αMHC-Cre Fgf21-/-	8 Weeks	TAC

Showing results 1 to 40 of 40

Showing results 1 to 40 of 40

Collection:

Collection ID:	CO003978
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:	TR003994
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:

TR003994

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:	SP003991
Sampleprep Summary:	For lipidomics analysis, the organic portion of extracted sample from two-phase extraction method was dried under nitrogen, resuspended in 200µL solvent (acetonitrile/isopropanol/water, 35/45/20 v/v/v with 10 mM ammonium formate and 0.1% formic acid), vortexed, sonicated, centrifuged and subsequently transferred an HPLC vial. An aliquot of 20 µl of chilled methanol containing an internal standard mixture (PE(17:0/17:0), PG(18:0/16:0)-d5, PC(18:1/16:0)-d31, Spingosine(17:0), Ceramide(d18:1/17:0); SM (d18:1/17:0); Palmitic acid-d3; Cholesterol-d7; TG (17:0/17:1/17:0)-d5; DG (12:0/12:0/0:0); MG (17:0/0:0/0:0); LPS(17:0), LPE (17:1)) was added to each sample. The untargeted lipidomics analysis was conducted on a Q ExactiveTM plus hybrid quadrupole-OrbitrapTM mass spectrometer interfaced with Vanquish ultra-high performance liquid chromatography (UHPLC) system (Thermo Scientific, Waltham, MA). A gradient mobile phase was used with a binary solvent system, which changed from 60% solvent A to 57% solvent A over 2 min, then to 50% solvent A at 2.1 min, then to 46% solvent A over 9.9 min, and then, after change to 30% at 12.1 min, to 1% solvent A over 5.9 min, then to 60% solvent A at 18.1 min and this was held for 2 min. The total run time was 20 min, and the flow rate was 0.4 mL/min. Solvent A consisted of acetonitrile/water (60/40) with 10 mM ammonium formate and 0.1% formic acid; solvent B consisted of isopropanol/acetonitrile (90/10) with 10 mM ammonium formate and 0.1% formic acid. The injection volume was 5 μL for both negative and positive ion mode. An Acquity CSH C18 UPLC column (2.1 × 100 mm, 1.7 µm, Waters, Milford, MA) was used for separation. Column temperature was set at 55°C. The ESI source was operated in the following parameters: spray voltage is 2.5 KV, capillary temperature, 350°C; sheath gas flow rate, 35; auxiliary gas heater temperature, 325°C. Data were acquired using full MS scan (mass scan range 150-1500 m/z, AGC target 3e6, maximum IT 100 ms, resolution 140,000) and collision induced dissociation-based data dependent on MS/MS (resolution 17,500, AGC target 1e5, maximum IT 50 ms, loop count 15, top N =15, isolation window 1.0 m/z, stepped NCE 20, 40, 60). Data quality and instrument performance was monitored throughout the data acquisition using quality control (internal standards), method blanks and pooled samples.

Sampleprep ID:

SP003991

Sampleprep Summary:

For lipidomics analysis, the organic portion of extracted sample from two-phase extraction method was dried under nitrogen, resuspended in 200µL solvent (acetonitrile/isopropanol/water, 35/45/20 v/v/v with 10 mM ammonium formate and 0.1% formic acid), vortexed, sonicated, centrifuged and subsequently transferred an HPLC vial. An aliquot of 20 µl of chilled methanol containing an internal standard mixture (PE(17:0/17:0), PG(18:0/16:0)-d5, PC(18:1/16:0)-d31, Spingosine(17:0), Ceramide(d18:1/17:0); SM (d18:1/17:0); Palmitic acid-d3; Cholesterol-d7; TG (17:0/17:1/17:0)-d5; DG (12:0/12:0/0:0); MG (17:0/0:0/0:0); LPS(17:0), LPE (17:1)) was added to each sample. The untargeted lipidomics analysis was conducted on a Q ExactiveTM plus hybrid quadrupole-OrbitrapTM mass spectrometer interfaced with Vanquish ultra-high performance liquid chromatography (UHPLC) system (Thermo Scientific, Waltham, MA). A gradient mobile phase was used with a binary solvent system, which changed from 60% solvent A to 57% solvent A over 2 min, then to 50% solvent A at 2.1 min, then to 46% solvent A over 9.9 min, and then, after change to 30% at 12.1 min, to 1% solvent A over 5.9 min, then to 60% solvent A at 18.1 min and this was held for 2 min. The total run time was 20 min, and the flow rate was 0.4 mL/min. Solvent A consisted of acetonitrile/water (60/40) with 10 mM ammonium formate and 0.1% formic acid; solvent B consisted of isopropanol/acetonitrile (90/10) with 10 mM ammonium formate and 0.1% formic acid. The injection volume was 5 μL for both negative and positive ion mode. An Acquity CSH C18 UPLC column (2.1 × 100 mm, 1.7 µm, Waters, Milford, MA) was used for separation. Column temperature was set at 55°C. The ESI source was operated in the following parameters: spray voltage is 2.5 KV, capillary temperature, 350°C; sheath gas flow rate, 35; auxiliary gas heater temperature, 325°C. Data were acquired using full MS scan (mass scan range 150-1500 m/z, AGC target 3e6, maximum IT 100 ms, resolution 140,000) and collision induced dissociation-based data dependent on MS/MS (resolution 17,500, AGC target 1e5, maximum IT 50 ms, loop count 15, top N =15, isolation window 1.0 m/z, stepped NCE 20, 40, 60). Data quality and instrument performance was monitored throughout the data acquisition using quality control (internal standards), method blanks and pooled samples.

Chromatography:

Chromatography ID:	CH004800
Instrument Name:	Thermo Vanquish
Column Name:	Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um)
Column Temperature:	55
Flow Gradient:	0.0 min – 60% A 2.0 min – 57% A 2.1 min – 50% A 12.0 min – 46% A 12.1 min – 30% A 18.0 min – 1% A 18.1–20.0 min – 60% A
Flow Rate:	0.4 mL/min
Solvent A:	60% Acetonitrile/40% Water; 10 mM ammonium formate; 0.1% formic acid
Solvent B:	90% Isopropanol/10% Acetonitrile; 10 mM ammonium formate; 0.1% formic acid
Chromatography Type:	Reversed phase

Analysis:

Analysis ID:	AN006328
Analysis Type:	MS
Chromatography ID:	CH004800
Has Mz:	1
Has Rt:	1
Rt Units:	Minutes
Results File:	ST003851_AN006328_Results.txt
Units:	A.U.

Analysis ID:	AN006329
Analysis Type:	MS
Chromatography ID:	CH004800
Has Mz:	1
Has Rt:	1
Rt Units:	Minutes
Results File:	ST003851_AN006329_Results.txt
Units:	A.U.