Evidence map›Paper›PMID 34494556›Full record

ArticleJCI insight2021

Lipin 1 modulates mRNA splicing during fasting adaptation in liver.

Huan Wang, Tracey W Chan, Ajay A Vashisht, Brian G Drew, Anna C Calkin, Thurl E Harris, James A Wohlschlegel, Xinshu Xiao, Karen Reue

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 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Role of lipins in cardiovascular diseases.Lipids in health and disease · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. The AMPK pathway in fatty liver disease.Frontiers in physiology · 2022
    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

9 authors at 4 institutions in 3 countries.

Huan WangHuman Genetics, David Geffen School of Medicine at UCLA,
Tracey W ChanBioinformatics Interdepartmental Program and.
Ajay A VashishtBiological Chemistry, University of California, Los Angeles, California, USA.
Brian G DrewBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Anna C CalkinBaker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Thurl E HarrisPharmacology, University of Virginia, Charlottesville, Virginia, USA.
James A WohlschlegelBiological Chemistry, University of California, Los Angeles, California, USA.
Xinshu XiaoBioinformatics Interdepartmental Program and.
Karen ReueHuman Genetics, David Geffen School of Medicine at UCLA,
University of California, Los Angeles · USBaker Heart and Diabetes Institute · AUInstitute of Human Genetics · PLUniversity of Virginia · US

Funding

Systems genomics of metabolic syndrome traitsP01HL028481 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 1985 to 2019
$50.2M
The Lipin Protein Family and Triglyceride Metabolism P01HL090553 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2008 to 2018
$23.3M
Proteolytic Control of Iron Metabolism by the Ubiquitin Ligase FBXL5R01GM089778 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WOHLSCHLEGEL, JAMES AKIRA · 2010 to 2023
$4.0M
Prioritization of splicing-altering genetic variants in Alzheimer's diseaseR01AG056476 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI XIAO, XINSHU GRACE · 2017 to 2021
$2.0M
Regulation of lipin phosphatidic acid phosphatase activityR01GM136900 · NIGMS · UNIVERSITY OF VIRGINIA · PI HARRIS, THURL E. · 2020 to 2023
$1.4M
NHLBI NIH HHS P01 HL028481NHLBI NIH HHS P01 HL090553NIA NIH HHS R01 AG056476NIGMS NIH HHS R01 GM089778NIGMS NIH HHS R01 GM136900
6 · The paper itself

Abstract

Lipin 1 regulates cellular lipid homeostasis through roles in glycerolipid synthesis (through phosphatidic acid phosphatase activity) and transcriptional coactivation. Lipin 1-deficient individuals exhibit episodic disease symptoms that are triggered by metabolic stress, such as stress caused by prolonged fasting. We sought to identify critical lipin 1 activities during fasting. We determined that lipin 1 deficiency induces widespread alternative mRNA splicing in liver during fasting, much of which is normalized by refeeding. The role of lipin 1 in mRNA splicing was largely independent of its enzymatic function. We identified interactions between lipin 1 and spliceosome proteins, as well as a requirement for lipin 1 to maintain homeostatic levels of spliceosome small nuclear RNAs and specific RNA splicing factors. In fasted Lpin1-/- liver, we identified a correspondence between alternative splicing of phospholipid biosynthetic enzymes and dysregulated phospholipid levels; splicing patterns and phospholipid levels were partly normalized by feeding. Thus, lipin 1 influences hepatic lipid metabolism through mRNA splicing, as well as through enzymatic and transcriptional activities, and fasting exacerbates the deleterious effects of lipin 1 deficiency on metabolic homeostasis.

Indexed as

Adaptation, PhysiologicalAlternative SplicingAnimalsCells, CulturedFastingFemaleHumansLipid MetabolismLiverMaleMiceMice, Inbred BALB CModels, AnimalPhosphatidate PhosphataseRNA, MessengerRNA SplicingLpin1 protein, mousePhosphatidate PhosphataseRNA, MessengerTranscription FactorsGenetic diseasesMetabolismMolecular biologyMouse models

Identifiers

PMID34494556
PMCPMC8492312
OpenAlexW3196742139

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.