Evidence map›Paper›PMID 40245984›Full record

ArticleJournal of lipid research2025

PPARɑ variant V227A reduces plasma triglycerides through enhanced lipoprotein lipolysis.

Lauren F Uchiyama, Gabriel P M Ordonez, Khoi T Pham, John P Kennelly, Maykel López Rodríguez, Lany Tran, Peter Tontonoz, Alexander Nguyen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of lipid research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

8 authors.

Lauren F UchiyamaDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA; Department of Biological Chemistry, University of California, Los Angeles, CA.
Gabriel P M OrdonezVatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.
Khoi T PhamVatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.
John P KennellyDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA; Department of Biological Chemistry, University of California, Los Angeles, CA.
Maykel López RodríguezDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA; Department of Biological Chemistry, University of California, Los Angeles, CA.
Lany TranVatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.
Peter TontonozDepartment of Pathology and Laboratory Medicine, University of California, Los Angeles, CA; Department of Biological Chemistry, University of California, Los Angeles, CA.
Alexander NguyenVatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA. Electronic address: alexannguyen@mednet.ucla.edu.

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
GASTROENTEROLOGYT32DK007180 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JENSEN, DENNIS MICHAEL · 1986 to 2025
$10.0M
Lipid storage and utilization in physiology and obesityR01DK136150 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PETER J TONTONOZ · 2023 to 2026
$2.2M
Role of a Novel Methyltransferase in Liver Lipid MetabolismK08DK136706 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Alexander Nguyen · 2024 to 2026
$587k
Regulation of hepatic lipid metabolism by novel protein BASICF30DK134050 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI UCHIYAMA, LAUREN F · 2022 to 2025
$186k
NIDDK NIH HHS F30 DK134050NIDDK NIH HHS K08 DK136706NIDDK NIH HHS R01 DK136150NIDDK NIH HHS T32 DK007180NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

Human single nucleotide variants in peroxisome proliferator-activated receptor-ɑ (PPARɑ) have been associated with beneficial metabolic phenotypes, yet their specific effects on metabolic gene expression are not well defined. Here, we developed a mouse model of a human PPARɑ variant encoding a substitution of valine for alanine at position 227 (V227A) to explore the role of this variant on systemic metabolism. Substitution with this variant in mice reduced plasma triglycerides, without altering body mass or liver lipid accumulation, consistent with phenotypes observed in human cohorts. Gene expression analysis revealed that the V227A variant enhances Ppara target gene expression in mouse liver, consistent with the effects of synthetic PPARɑ agonist treatment. Notably, V227A increased hepatic expression of Lpl, the predominant enzyme responsible for circulating triglyceride hydrolysis. Further characterization revealed that heart tissue from variant mice exhibited increased Lpl expression and triglyceride hydrolysis activity, suggesting that V227A enhances cardiac triglyceride clearance. These findings validate human observational studies and clarify the physiological impact of the V227A PPARɑ variant on plasma triglycerides.

Indexed as

LipolysisLipoproteinsPPAR alphaTriglyceridesAnimalsHumansLipoprotein LipaseLiverMaleMiceMice, Inbred C57BLPolymorphism, Single NucleotideLipoprotein LipaseLipoproteinsPPAR alphaTriglycerideslipolysis and fatty acid metabolismlipoprotein lipaseliverPPARstriglycerides

Identifiers

PMID40245984
PMCPMC12144439

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.