Evidence map›Paper›PMID 39739772›Full record

ArticlePloS one2024

Loss of Mfn1 but not Mfn2 enhances adipogenesis.

Jake P Mann, Luis Carlos Tábara, Satish Patel, Pushpa Pushpa, Anna Alvarez-Guaita, Liang Dong, Afreen Haider, Koini Lim, Panna Tandon, Fabio Scurria and 6 more

Abstract read
In one paragraph

Article in PloS one, 2024. 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
–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

4 citing papers in PubMed.

  1. Article
  2. Article
  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

16 authors.

Jake P MannMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Luis Carlos TábaraMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United Kingdom.
Satish PatelMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Pushpa PushpaMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Anna Alvarez-GuaitaMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Liang DongMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Afreen HaiderMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Koini LimMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Panna TandonCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
Fabio ScurriaMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
James E N MinchinCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.
Stephen O'Rahilly SMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Daniel J FazakerleyMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.ORCID 0000-0001-8241-2903
Julien PrudentMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United Kingdom.
Robert K SempleCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom.ORCID 0000-0001-6539-3069
David B SavageMetabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.

Funding

Medical Research Council MC_UU_00015/7Wellcome Trust
6 · The paper itself

Abstract

objectiveA biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles in adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact of loss of mitofusin 1 (Mfn1) or 2 (Mfn2) on adipogenesis in cultured cells.

methodsWe characterised adipocyte differentiation of wildtype (WT), Mfn1-/- and Mfn2-/- mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes in which Mfn1 or 2 levels were reduced using siRNA.

resultsMfn1-/- MEFs displayed striking fragmentation of the mitochondrial network, with surprisingly enhanced propensity to differentiate into adipocytes, as assessed by lipid accumulation, expression of adipocyte markers (Plin1, Fabp4, Glut4, Adipoq), and insulin-stimulated glucose uptake. RNA sequencing revealed a corresponding pro-adipogenic transcriptional profile including Pparg upregulation. Mfn2-/- MEFs also had a disrupted mitochondrial morphology, but in contrast to Mfn1-/- MEFs they showed reduced expression of adipocyte markers. Mfn1 and Mfn2 siRNA mediated knockdown studies in 3T3-L1 adipocytes generally replicated these findings.

conclusionsLoss of Mfn1 but not Mfn2 in cultured pre-adipocyte models is pro-adipogenic. This suggests distinct, non-redundant roles for the two mitofusin orthologues in adipocyte differentiation.

Indexed as

3T3-L1 CellsAdipocytesAdipogenesisFibroblastsGTP PhosphohydrolasesMitochondriaAnimalsCell DifferentiationFatty Acid-Binding ProteinsMiceMice, KnockoutPPAR gammaFatty Acid-Binding ProteinsGTP PhosphohydrolasesMfn1 protein, mouseMfn2 protein, mousePPAR gamma

Identifiers

PMID39739772
PMCPMC11687706

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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.