Evidence map›Paper›PMID 34473251›Full record

ArticleEndocrinology2021

The Role of Mitochondria-Linked Fatty-Acid Uptake-Driven Adipogenesis in Graves Orbitopathy.

Lei Zhang, Pavandeep Rai, Satomi Miwa, Mohd Shazli Draman, D Aled Rees, Anjana S Haridas, Daniel S Morris, Andrew R Tee, Marian Ludgate, Doug M Turnbull and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  2. Review
  3. Orbital Signaling in Graves' Orbitopathy.Frontiers in endocrinology · 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

11 authors at 4 institutions in 1 country.

Lei ZhangSchool of Medicine, Cardiff University, Heath Park Hospital, Cardiff, CF14 4XN, UK.ORCID 0000-0003-3536-8692
Pavandeep RaiWellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, NE2 4HH, UK.
Satomi MiwaBiosciences Institute, Newcastle University, Newcastle Upon Tyne, NE4 5PL, UK.
Mohd Shazli DramanSchool of Medicine, Cardiff University, Heath Park Hospital, Cardiff, CF14 4XN, UK.
D Aled ReesSchool of Medicine, Cardiff University, Heath Park Hospital, Cardiff, CF14 4XN, UK.
Anjana S HaridasDepartment of Ophthalmology, Cardiff & Vale University Health Board, Heath Park Hospital , Cardiff CF14 4XW, UK.
Daniel S MorrisDepartment of Ophthalmology, Cardiff & Vale University Health Board, Heath Park Hospital , Cardiff CF14 4XW, UK.
Andrew R TeeSchool of Medicine, Cardiff University, Heath Park Hospital, Cardiff, CF14 4XN, UK.
Marian LudgateSchool of Medicine, Cardiff University, Heath Park Hospital, Cardiff, CF14 4XN, UK.
Doug M TurnbullWellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, NE2 4HH, UK.
Colin M DayanSchool of Medicine, Cardiff University, Heath Park Hospital, Cardiff, CF14 4XN, UK.
University Hospital of Wales · GBCardiff and Vale University Health Board · GBWellcome Centre for Mitochondrial Research · GBNewcastle University · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextDepot-specific expansion of orbital adipose tissue (OAT) in Graves orbitopathy (GO; an autoimmune condition producing proptosis, visual impairment and reduced quality of life) is associated with fatty acid (FA)-uptake-driven adipogenesis in preadipocytes/fibroblasts (PFs).

objectiveThis work sought a role for mitochondria in OAT adipogenesis in GO.

methodsConfluent PFs from healthy OAT (OAT-H), OAT from GO (OAT-GO) and white adipose tissue in culture medium compared with culture medium containing a mixed hormonal cocktail as adipogenic medium (ADM), or culture-medium containing FA-supplementation, oleate:palmitate:linoleate (45:30:25%) with/without different concentration of mitochondrial biosubstrate adenosine 5'-diphosphate/guanosine 5'-diphosphate (ADP/GDP), AICAR (adenosine analogue), or inhibitor oligomycin-A for 17 days. Main outcome measures included oil-red-O staining and foci count of differentiated adipocytes for in vitro adipogenesis, flow cytometry, relative quantitative polymerase chain reaction, MTS-assay/106 cells, total cellular-ATP detection kit, and Seahorse-XFe96-Analyzer for mitochondria and oxidative-phosphorylation (OXPHOS)/glycolysis-ATP production analysis.

resultsDuring early adipogenesis before adipocyte formation (days 0, 4, and7), we observed OAT-specific cellular ATP production via mitochondrial OXPHOS in PFs both from OAT-H and OAT-GO, and substantially disrupted OXPHOS-ATP/glycolysis-ATP production in PFs from OAT-GO, for example, a 40% reduction in OXPHOS-ATP and trend-increased glycolysis-ATP production on days 4 and 7 compared with day 0, which contrasted with the stable levels in OAT-H. FA supplementation in culture-medium triggered adipogenesis in PFs both from OAT-H and OAT-GO, which was substantially enhanced by 1-mM GDP reaching 7% to 18% of ADM adipogenesis. The FA-uptake-driven adipogenesis was diminished by oligomycin-A but unaffected by treatment with ADP or AICAR. Furthermore, we observed a significant positive correlation between FA-uptake-driven adipogenesis by GDP and the ratios of OXPHOS-ATP/glycolysis-ATP through adipogenesis of PFs from OAT-GO.

conclusionOur study confirmed that FA uptake can drive OAT adipogenesis and revealed a fundamental role for mitochondria-OXPHOS in GO development, which provides potential for therapeutic interventions.

Indexed as

AdipocytesAdipogenesisAdipose TissueCell DifferentiationCells, CulturedFatty AcidsFibroblastsGraves OphthalmopathyHumansLipid MetabolismMitochondriaOrbitOxidative PhosphorylationFatty AcidsadipogenesisATP productionfatty acid uptakeGraves orbitopathymitochondria OXPHOSorbital adipose tissue

Identifiers

PMID34473251
PMCPMC8848742
OpenAlexW3198221021

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.