Evidence map›Paper›PMID 34074713›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2021

Liver-Specific Nonviral Gene Delivery of Fibroblast Growth Factor 21 Protein Expression in Mice Regulates Body Mass and White/Brown Fat Respiration.

Nathaniel G Girer, Victoria G Rontoyanni, Aditya Joshi, Igor Patrikeev, Andrew J Murton, Craig Porter, Massoud Motamedi, Cornelis J Elferink

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 48% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. 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 at 4 institutions in 1 country.

Nathaniel G GirerDepartment of Pharmacology and Toxicology (N.G.G., A.J., C.J.E.), Metabolism Unit, Department of Surgery (V.G.R., A.J.M., C.P.), Department of Ophthalmology and Visual Sciences, Center for Biomedical Engineering (I.P., M.M.), Sealy Center of Aging (V.G.R., A.J.M.), The University of Texas Medical Branch at Galveston, Galveston, Texas; Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (A.J.); and Division of Developmental Nutrition, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.P.).
Victoria G RontoyanniDepartment of Pharmacology and Toxicology (N.G.G., A.J., C.J.E.), Metabolism Unit, Department of Surgery (V.G.R., A.J.M., C.P.), Department of Ophthalmology and Visual Sciences, Center for Biomedical Engineering (I.P., M.M.), Sealy Center of Aging (V.G.R., A.J.M.), The University of Texas Medical Branch at Galveston, Galveston, Texas; Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (A.J.); and Division of Developmental Nutrition, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.P.).
Aditya JoshiDepartment of Pharmacology and Toxicology (N.G.G., A.J., C.J.E.), Metabolism Unit, Department of Surgery (V.G.R., A.J.M., C.P.), Department of Ophthalmology and Visual Sciences, Center for Biomedical Engineering (I.P., M.M.), Sealy Center of Aging (V.G.R., A.J.M.), The University of Texas Medical Branch at Galveston, Galveston, Texas; Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (A.J.); and Division of Developmental Nutrition, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.P.).
Igor PatrikeevDepartment of Pharmacology and Toxicology (N.G.G., A.J., C.J.E.), Metabolism Unit, Department of Surgery (V.G.R., A.J.M., C.P.), Department of Ophthalmology and Visual Sciences, Center for Biomedical Engineering (I.P., M.M.), Sealy Center of Aging (V.G.R., A.J.M.), The University of Texas Medical Branch at Galveston, Galveston, Texas; Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (A.J.); and Division of Developmental Nutrition, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.P.).
Andrew J MurtonDepartment of Pharmacology and Toxicology (N.G.G., A.J., C.J.E.), Metabolism Unit, Department of Surgery (V.G.R., A.J.M., C.P.), Department of Ophthalmology and Visual Sciences, Center for Biomedical Engineering (I.P., M.M.), Sealy Center of Aging (V.G.R., A.J.M.), The University of Texas Medical Branch at Galveston, Galveston, Texas; Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (A.J.); and Division of Developmental Nutrition, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.P.).
Craig PorterDepartment of Pharmacology and Toxicology (N.G.G., A.J., C.J.E.), Metabolism Unit, Department of Surgery (V.G.R., A.J.M., C.P.), Department of Ophthalmology and Visual Sciences, Center for Biomedical Engineering (I.P., M.M.), Sealy Center of Aging (V.G.R., A.J.M.), The University of Texas Medical Branch at Galveston, Galveston, Texas; Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (A.J.); and Division of Developmental Nutrition, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.P.).
Massoud MotamediDepartment of Pharmacology and Toxicology (N.G.G., A.J., C.J.E.), Metabolism Unit, Department of Surgery (V.G.R., A.J.M., C.P.), Department of Ophthalmology and Visual Sciences, Center for Biomedical Engineering (I.P., M.M.), Sealy Center of Aging (V.G.R., A.J.M.), The University of Texas Medical Branch at Galveston, Galveston, Texas; Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (A.J.); and Division of Developmental Nutrition, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.P.).
Cornelis J ElferinkDepartment of Pharmacology and Toxicology (N.G.G., A.J., C.J.E.), Metabolism Unit, Department of Surgery (V.G.R., A.J.M., C.P.), Department of Ophthalmology and Visual Sciences, Center for Biomedical Engineering (I.P., M.M.), Sealy Center of Aging (V.G.R., A.J.M.), The University of Texas Medical Branch at Galveston, Galveston, Texas; Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (A.J.); and Division of Developmental Nutrition, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas (C.P.) coelferi@utmb.edu.
The University of Texas Medical Branch at Galveston · USUniversity of Arkansas for Medical Sciences · USTexas A&M University at Galveston · USUniversity of Oklahoma Health Sciences Center · US

Funding

UTMB OAIC Research Education Component (REC)P30AG024832 · NIA · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI JAMES S. GOODWIN, MD, MELISSA M. MORROW · 2005 to 2026
$26.7M
Translational Research Support CoreP30ES030285 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Fernanda Laezza, Cheryl L. Walker · 2019 to 2026
$14.7M
Novel Mechanism of aryl hydrocarbon receptor-mediated differential gene regulationR01DK122028 · NIDDK · UNIVERSITY OF TEXAS MED BR GALVESTON · PI Aditya D Joshi · 2019 to 2026
$2.3M
Aryl Hydrocarbon Receptor-Mediated Epigenetic ProcessesR01ES026874 · NIEHS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI ELFERINK, CORNELIS JOHAN · 2016 to 2020
$2.2M
Mechanistic Insights into Aryl Hydrocarbon Receptor Regulation of Fibroblast Growth Factor 21 and its Influence on Systemic Energy MetabolismF32DK116489 · NIDDK · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GIRER, NATHANIEL · 2019 to 2019
$61k
NIA NIH HHS P30 AG024832NIDDK NIH HHS F32 DK116489NIDDK NIH HHS R01 DK122028NIEHS NIH HHS P30 ES030285NIEHS NIH HHS R01 ES026874
6 · The paper itself

Abstract

Viral-mediated in vivo gene delivery methods currently dominate among therapeutic strategies within the clinical and experimental settings, albeit with well documented limitations arising from immunologic constraints. In this study, we demonstrate the utility of nonviral hepatotropic in vivo gene delivery of unpackaged expression constructs, including one encoding fibroblast growth factor 21 (FGF21). FGF21 is an important hepatokine whose expression positively correlates with therapeutic outcomes across various animal models of obesity. Our data demonstrate that FGF21 expression can be restored into the livers of immunocompetent FGF21 knockout mice for at least 2 weeks after a single injection with an FGF21 expression plasmid. In wild-type C57BL6/J mice, in vivo transfection with an FGF21-expressing plasmid induced weight loss, decreased adiposity, and activated thermogenesis in white fat within 2 weeks. Furthermore, in vivo FGF21 gene delivery protected C57BL6/J mice against diet-induced obesity by decreasing adiposity and increasing uncoupling protein 1-dependent thermogenesis in brown fat and by boosting respiratory capacity in subcutaneous and perigonadal white fat. Together, the data illustrate a facile and effective methodology for delivering prolonged protein expression specifically to the liver. We contend that this method will find utility in basic science research as a practical means to enhance in vivo studies characterizing liver protein function. We further believe our data provide a rationale for further exploring the potential clinical utility of nonviral gene therapy in mouse models of disease. SIGNIFICANCE STATEMENT: This study presents a valuable method for nonviral gene delivery in mice that improves upon existing techniques. The data provide a rationale for further exploring the potential clinical utility of nonviral gene therapy in mouse models of disease and will likely enhance in vivo studies characterizing liver protein function.

Indexed as

Adipose Tissue, BrownAdipose Tissue, WhiteFibroblast Growth FactorsGene Transfer TechniquesLiverMice, Inbred C57BLThermogenesisAnimalsBody WeightDiet, High-FatMaleMiceMice, KnockoutObesityRespirationfibroblast growth factor 21Fibroblast Growth Factors

Identifiers

PMID34074713
PMCPMC8686718
OpenAlexW3165616511

What Socratic 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 Socratic graph.