Evidence map›Paper›PMID 33594826›Full record

ArticleObesity (Silver Spring, Md.)2021

Inhibition of PAI-1 Promotes Lipolysis and Enhances Weight Loss in Obese Mice.

Joshua A Levine, Shantel Olivares, Toshio Miyata, Douglas E Vaughan, Anne S Henkel

Open access · greenAbstract read
In one paragraph

Article in Obesity (Silver Spring, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Efficacy of Probiotic StrainsPharmaceuticals (Basel, Switzerland) · 2024
    Article
  8. Review
  9. Review
  10. Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?International journal of molecular sciences · 2021
    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

5 authors at 2 institutions in 2 countries.

Joshua A LevineDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Shantel OlivaresDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Toshio MiyataDepartment of Molecular Medicine and Therapy, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan.
Douglas E VaughanDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Anne S HenkelDepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.ORCID 0000-0001-8253-1507
Northwestern University · USTohoku University · JP

Funding

Pleiotropic Role of PAI-1 in Cardiovascular AgingR01HL051387 · NHLBI · VANDERBILT UNIVERSITY · PI VAUGHAN, DOUGLAS E · 1994 to 2023
$7.9M
TRAINING IN METABOLISM, DIABETES AND ENDOCRINOLOGYT32DK007169 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Joseph Bass · 1988 to 2026
$6.6M
Spontaneous cardiac fibrosis in PAI-1-deficient mice and men: A rare mutation informs a common molecular pathophysiologyR01HL142761 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI VAUGHAN, DOUGLAS E · 2019 to 2022
$2.6M
The Role of PAI-1 and Circadian Disruption in the Pathogenesis of NASHK08DK095992 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HENKEL, ANNE S · 2013 to 2017
$621k
Molecular Mechanisms of Nonalcoholic Fatty Liver DiseaseI01BX003854 · VA · JESSE BROWN VA MEDICAL CENTER · PI HENKEL, ANNE S · 2017 to 2020
–
BLRD VA I01 BX003854NHLBI NIH HHS R01 HL051387NHLBI NIH HHS R01 HL142761NIDDK NIH HHS K08 DK095992NIDDK NIH HHS T32 DK007169NIDDK NIH HHS T32DK007169
6 · The paper itself

Abstract

objectiveThis study investigates the therapeutic potential of a small molecule inhibitor of plasminogen activator inhibitor-1 (PAI-1), TM5441, in reversing diet-induced obesity in mice.

methodsWild-type C57BL/6J mice were fed a high-fat high-sugar (HFHS) diet for 8 weeks to induce obesity. After the first 8 weeks, TM5441 was added to the diet for an additional 8 weeks. In order to determine the efficacy of PAI-1 inhibition in conjunction with dietary modification, mice were fed an HFHS diet for 8 weeks to induce obesity and were then switched to a low-fat diet with or without TM5441 for an additional 2 to 8 weeks.

resultsObese mice showed weight reduction and significant improvement in hepatic steatosis when TM5441 was added to the HFHS diet. Obese mice that were treated with TM5441 in conjunction with dietary modification showed enhanced weight loss and a more rapid reversal of hepatic steatosis compared with obese mice treated with dietary modification alone. The enhanced weight loss among mice treated with TM5441 was associated with increased adipose tissue expression of adipose triglyceride lipase, phosphorylated hormone-sensitive lipase, and phosphorylated perilipin-1 as well as induction of adipose tissue lipolysis.

conclusionsPharmacologic PAI-1 inhibition stimulates adipose tissue lipolysis and enhances weight loss in obese mice.

Indexed as

AnimalsLipolysisMaleMiceMice, ObesePlasminogen Activator Inhibitor 1Weight LossPlasminogen Activator Inhibitor 1

Identifiers

PMID33594826
PMCPMC8842994
OpenAlexW3131283278

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.