Evidence map›Paper›PMID 33986192›Full record

ArticleJCI insight2021

Myocardial Lipin 1 knockout in mice approximates cardiac effects of human LPIN1 mutations.

Kari T Chambers, Michael A Cooper, Alison R Swearingen, Rita T Brookheart, George G Schweitzer, Carla J Weinheimer, Attila Kovacs, Timothy R Koves, Deborah M Muoio, Kyle S McCommis and 1 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Lipid Ratios for Diagnosis and Prognosis of Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2025
    Article
  5. Article
  6. Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  7. Lipotoxicity as a therapeutic target in obesity and diabetic cardiomyopathy.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2024
    Review
  8. Role of lipins in cardiovascular diseases.Lipids in health and disease · 2023
    Review
  9. Article
  10. Article
  11. Momordicine I alleviates isoproterenol-induced cardiomyocyte hypertrophy through suppression of PLA2G6 and DGK-ζ.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023
    Article
  12. Article
  13. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Kari T ChambersDivision of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Michael A CooperDivision of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Alison R SwearingenDivision of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Rita T BrookheartDivision of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
George G SchweitzerDivision of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Carla J WeinheimerDivision of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Attila KovacsDivision of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Timothy R KovesDuke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Departments of Medicine and Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA.
Deborah M MuoioDuke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Departments of Medicine and Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA.
Kyle S McCommisDepartment of Biochemistry & Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
Brian N FinckDivision of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Washington University in St. Louis · USDuke University · USSaint Louis University · US

Funding

Washington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Jeffrey Wade Brown · 2000 to 2026
$30.8M
Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Dominic N Reeds · 1999 to 2026
$30.2M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
Probing the Role of Mitochondrial Short-chain Carbon Homeostasis in the Hypertrophied and Failing HeartR01HL128349 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUOIO, DEBORAH M · 2016 to 2024
$6.1M
Training in Integrative and Systems Biology of Cardiovascular DiseaseT32HL134635 · NHLBI · WASHINGTON UNIVERSITY · PI NERBONNE, JEANNE M. · 2017 to 2021
$1.8M
Novel insulin-sensitizing NASH/diabetes drugs.R42DK121652 · NIDDK · BIOIO, LLC · PI FINCK, BRIAN N, PETERSON, TIMOTHY R · 2019 to 2022
$1.7M
Genetic Factors of Bone Loss in Older Adults Taking AntidepressantsR01AR073017 · NIAMS · WASHINGTON UNIVERSITY · PI PETERSON, TIMOTHY R · 2018 to 2021
$1.6M
LIPIN 1 AND CARDIAC METABOLISM IN THE CONTEXT OF LIPID OVERLOADR01HL119225 · NHLBI · WASHINGTON UNIVERSITY · PI FINCK, BRIAN N · 2014 to 2017
$1.5M
Importance and Regulation of Cardiac Mitochondrial Pyruvate TransportR00HL136658 · NHLBI · SAINT LOUIS UNIVERSITY · PI MCCOMMIS, KYLE S · 2019 to 2021
$747k
Site-1 Protease in the regulation of skeletal muscle metabolism and exercise enduranceK01HL145326 · NHLBI · WASHINGTON UNIVERSITY · PI BROOKHEART, RITA THOMAS · 2019 to 2023
$551k
HIGH-RESOLUTON ULTRASOUND SYSTEM FOR PHENOTYPIC EVALUATION OF THE CARDIOVASCULAR SYSTEM IN MICES10OD028597 · OD · WASHINGTON UNIVERSITY · PI KOVACS, ATTILA · 2020 to 2020
$378k
NHLBI NIH HHS K01 HL145326NHLBI NIH HHS R00 HL136658NHLBI NIH HHS R01 HL119225NHLBI NIH HHS R01 HL128349NHLBI NIH HHS T32 HL134635NIAMS NIH HHS R01 AR073017NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P30 DK052574NIDDK NIH HHS P30 DK056341NIDDK NIH HHS R42 DK121652NIH HHS S10 OD028597
6 · The paper itself

Abstract

Lipin 1 is a bifunctional protein that is a transcriptional regulator and has phosphatidic acid (PA) phosphohydrolase activity, which dephosphorylates PA to generate diacylglycerol. Human lipin 1 mutations lead to episodic rhabdomyolysis, and some affected patients exhibit cardiac abnormalities, including exercise-induced cardiac dysfunction and cardiac triglyceride accumulation. Furthermore, lipin 1 expression is deactivated in failing heart, but the effects of lipin 1 deactivation in myocardium are incompletely understood. We generated mice with cardiac-specific lipin 1 KO (cs-Lpin1-/-) to examine the intrinsic effects of lipin 1 in the myocardium. Cs-Lpin1-/- mice had normal systolic cardiac function but mild cardiac hypertrophy. Compared with littermate control mice, PA content was higher in cs-Lpin1-/- hearts, which also had an unexpected increase in diacylglycerol and triglyceride content. Cs-Lpin1-/- mice exhibited diminished cardiac cardiolipin content and impaired mitochondrial respiration rates when provided with pyruvate or succinate as metabolic substrates. After transverse aortic constriction-induced pressure overload, loss of lipin 1 did not exacerbate cardiac hypertrophy or dysfunction. However, loss of lipin 1 dampened the cardiac ionotropic response to dobutamine and exercise endurance in association with reduced protein kinase A signaling. These data suggest that loss of lipin 1 impairs cardiac functional reserve, likely due to effects on glycerolipid homeostasis, mitochondrial function, and protein kinase A signaling.

Indexed as

Disease Models, AnimalMiceAnimalsCardiolipinsCardiomegalyCardiotonic AgentsCyclic AMP-Dependent Protein KinasesDiglyceridesDobutamineExercise ToleranceMice, KnockoutMitochondria, HeartMyocardial ContractionMyocardiumPhosphatidate PhosphatasePhosphatidic AcidsCardiolipinsCardiotonic AgentsCyclic AMP-Dependent Protein KinasesDiglyceridesDobutamineLpin1 protein, mousePhosphatidate PhosphatasePhosphatidic AcidsPyruvic AcidSuccinic AcidTriglyceridesCardiologyCardiovascular diseaseIntermediary metabolismMetabolismMitochondria

Identifiers

PMID33986192
PMCPMC8262319
OpenAlexW3160714343

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.