Evidence map›Paper›PMID 24849394›Full record

ArticleInternational journal of obesity (2005)2015

Genetic ablation of macrohistone H2A1 leads to increased leanness, glucose tolerance and energy expenditure in mice fed a high-fat diet.

F Sheedfar, M Vermeer, V Pazienza, J Villarroya, F Rappa, F Cappello, G Mazzoccoli, F Villarroya, H van der Molen, M H Hofker and 2 more

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In one paragraph

Article in International journal of obesity (2005), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

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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

12 authors at 7 institutions in 5 countries.

F SheedfarDepartment of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
M VermeerDepartment of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
V PazienzaGastroenterology Unit, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy.
J Villarroya1] Department of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain [2] CIBER Fisiopatologia de la Obesidad y Nutricion, Instituto de Salud Carlos III, Madrid, Spain.
F RappaDepartment of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Palermo, Italy.
F Cappello1] Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Palermo, Italy [2] Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
G MazzoccoliDivision of Internal Medicine and Chronobiology Unit, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy.
F VillarroyaDepartment of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain.
H van der MolenDepartment of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
M H HofkerDepartment of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
D P KoonenDepartment of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands.
M Vinciguerra1] Gastroenterology Unit, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza' Hospital, San Giovanni Rotondo (FG), Italy [2] Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy [3] Institute for Liver and Digestive Health, Division of Medicine, University College London (UCL), UCL Medical School, Royal Free Hospital, London, UK.
University Medical Center Groningen · NLCasa Sollievo della Sofferenza · ITUniversity of Groningen · NLUniversity of Palermo · ITInstituto de Salud Carlos III · ESUniversitat de Barcelona · ESUniversity College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND/

objectivesIn the context of obesity, epigenetic mechanisms regulate cell-specific chromatin plasticity, perpetuating gene expression responses to nutrient excess. MacroH2A1, a variant of histone H2A, emerged as a key chromatin regulator sensing small nutrients during cell proliferation and differentiation. Mice genetically ablated for macroH2A1 (knockout (KO)) do not show overt phenotypes under a standard diet. Our objective was to analyse the in vivo role of macroH2A1 in response to nutritional excess.

methodsTwelve-week-old whole-body macroH2A1 KO male mice were given a high-fat diet (60% energy from lard) for 12 weeks until being killed, and examined for glucose and insulin tolerance, and for body fat composition. Energy expenditure was assessed using metabolic cages and by measuring the expression levels of genes involved in thermogenesis in the brown adipose tissue (BAT) or in adipogenesis in the visceral adipose tissue (VAT).

resultsUnder a chow diet, macroH2A1 KO mice did not differ from their wild-type (WT) littermates for body weight, and for sensitivity to glucose or insulin. However, KO mice displayed decreased heat production (P<0.05), and enhanced total activity during the night (P<0.01). These activities related to protection against diet-induced obesity in KO mice, which displayed decreased body weight owing to a specific decrease in fat mass (P<0.05), increased tolerance to glucose (P<0.05), and enhanced total activity during the day (P<0.05), compared with WT mice. KO mice displayed increased expression of thermogenic genes (Ucp1, P<0.05; Glut4, P<0.05; Cox4, P<0.01) in BAT and a decreased expression of adipogenic genes (Pparγ, P<0.05; Fabp4, P<0.05; Glut4, P<0.05) in VAT compared with WT mice, indicative of augmented energy expenditure.

conclusionsGenetic eviction of macroH2A1 confers protection against diet-induced obesity and metabolic derangements in mice. Inhibition of macroH2A1 might be a helpful strategy for epigenetic therapy of obesity.

Indexed as

Energy MetabolismAdipogenesisAdipose Tissue, BrownAnimalsCell LineDiet, High-FatDisease Models, AnimalHistonesInsulin ResistanceMiceModels, MolecularThinnessHistonesmacroH2A histone

Identifiers

PMID24849394
OpenAlexW2094298965

What OpenQuestion holds

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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.