Evidence map›Paper›PMID 38039287›Full record

ArticlePloS one2023

A medium-chain fatty acid analogue prevents hepatosteatosis and decreases inflammatory lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis.

Bennet S Cho, Scott C Fligor, Gillian L Fell, Jordan D Secor, Savas T Tsikis, Amy Pan, Lumeng J Yu, Victoria H Ko, Duy T Dao, Lorenzo Anez-Bustillos and 6 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.5field-weighted citation impact, top 36% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. 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

16 authors at 2 institutions in 2 countries.

Bennet S ChoVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.ORCID 0000-0002-1440-0019
Scott C FligorVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Gillian L FellVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Jordan D SecorVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Savas T TsikisVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Amy PanVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Lumeng J YuVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Victoria H KoVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Duy T DaoVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Lorenzo Anez-BustillosVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Thomas I HirschVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.
Jenny LundDepartment of Pharmacy, Section for Pharmacology and Pharmaceutical Biosciences, University of Oslo, Oslo, Norway.ORCID 0000-0002-0744-8268
Arild C RustanDepartment of Pharmacy, Section for Pharmacology and Pharmaceutical Biosciences, University of Oslo, Oslo, Norway.
David A FraserNorthSea Therapeutics, Amsterdam, Netherlands.
Kathleen M GuraHarvard Medical School, Boston, Massachusetts, United States of America.
Mark PuderVascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, United States of America.ORCID 0000-0002-7941-2926
Boston Children's Hospital · USUniversity of Oslo · NO

Funding

HARVARD-LONGWOOD RESEARCH TRAINING IN VASCULAR SURGERYT32HL007734 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI FERRAN, CHRISTIANE, LOGERFO, FRANK W · 1993 to 2023
$10.5M
RESEARCH TRAINING IN ALIMENTARY TRACT SURGERYT32DK007754 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI HODIN, RICHARD A. · 1997 to 2025
$6.5M
NHLBI NIH HHS T32 HL007734NIDDK NIH HHS T32 DK007754
6 · The paper itself

Abstract

backgroundParenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis.

methodsTwo in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro.

resultsIn the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both β- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake.

conclusionsSEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both β- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis.

Indexed as

Fatty LiverSoybean OilAnimalsCarbohydratesDisease Models, AnimalEmulsionsFat Emulsions, IntravenousFatty AcidsFish OilsHumansLiverMaleMiceParenteral NutritionTriglyceridesCarbohydratesEmulsionsFat Emulsions, IntravenousFatty AcidsFish OilsSoybean OilTriglycerides

Identifiers

PMID38039287
PMCPMC10691711
OpenAlexW4389234919

What OpenQuestion holds

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LicenceCC BY
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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.