Evidence map›Paper›PMID 28436964›Full record

ArticleNature cell biology2017

SWELL1 is a regulator of adipocyte size, insulin signalling and glucose homeostasis.

Yanhui Zhang, Litao Xie, Susheel K Gunasekar, Dan Tong, Anil Mishra, William J Gibson, Chuansong Wang, Trevor Fidler, Brodie Marthaler, Aloysius Klingelhutz and 5 more

Erratum issuedOpen access · greenAbstract readVideo-Audio Media
In one paragraph

Article in Nature cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

111 citing papers in PubMed, 168 citations in OpenAlex.

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51 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 1 country.

Yanhui ZhangDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Litao XieDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Susheel K GunasekarDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Dan TongDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Anil MishraDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
William J GibsonHarvard Medical School, Boston, Massachusetts 02115, USA.
Chuansong WangDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio 43210, USA.
Trevor FidlerFraternal Order of Eagles Diabetes Research Center, Iowa City, Iowa 52242, USA.
Brodie MarthalerDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Aloysius KlingelhutzDepartment of Microbiology, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
E Dale AbelFraternal Order of Eagles Diabetes Research Center, Iowa City, Iowa 52242, USA.
Isaac SamuelDepartment of Surgery, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Jessica K SmithDepartment of Surgery, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
Lei CaoDepartment of Cancer Biology and Genetics, The Ohio State University, Columbus, Ohio 43210, USA.
Rajan SahDepartment of Internal Medicine, Division of Cardiovascular Medicine, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
University of Iowa · USFraternal Order of Eagles · USThe Ohio State University · USHarvard University · US

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Tuning fat cell size and obesity through SWELL1R01DK106009 · NIDDK · WASHINGTON UNIVERSITY · PI SAH, RAJAN · 2016 to 2024
$3.8M
Cancer Prevention and Treatment by Activation of a Brain-Adipocyte AxisR01CA166590 · NCI · OHIO STATE UNIVERSITY · PI CAO, LEI · 2013 to 2022
$3.4M
The role of hypothalamic-sympathoneural-adipocyte axis in healthy agingR01AG041250 · NIA · OHIO STATE UNIVERSITY · PI CAO, LEI · 2013 to 2017
$1.6M
Identifying brain mediators distinguishing eustress and distress impact on cancerR01CA163640 · NCI · OHIO STATE UNIVERSITY · PI CAO, LEI · 2013 to 2017
$1.2M
Modulating cancer progression by adipogenic human adenovirus type 36R21CA178227 · NCI · OHIO STATE UNIVERSITY · PI CAO, LEI · 2013 to 2014
$375k
NCI NIH HHS P30 CA086862NCI NIH HHS R01 CA163640NCI NIH HHS R01 CA166590NCI NIH HHS R21 CA178227NIA NIH HHS R01 AG041250NIDDK NIH HHS R01 DK106009NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Adipocytes undergo considerable volumetric expansion in the setting of obesity. It has been proposed that such marked increases in adipocyte size may be sensed via adipocyte-autonomous mechanisms to mediate size-dependent intracellular signalling. Here, we show that SWELL1 (LRRC8a), a member of the Leucine-Rich Repeat Containing protein family, is an essential component of a volume-sensitive ion channel (VRAC) in adipocytes. We find that SWELL1-mediated VRAC is augmented in hypertrophic murine and human adipocytes in the setting of obesity. SWELL1 regulates adipocyte insulin-PI3K-AKT2-GLUT4 signalling, glucose uptake and lipid content via SWELL1 C-terminal leucine-rich repeat domain interactions with GRB2/Cav1. Silencing GRB2 in SWELL1 KO adipocytes rescues insulin-pAKT2 signalling. In vivo, shRNA-mediated SWELL1 knockdown and adipose-targeted SWELL1 knockout reduce adiposity and adipocyte size in obese mice while impairing systemic glycaemia and insulin sensitivity. These studies identify SWELL1 as a cell-autonomous sensor of adipocyte size that regulates adipocyte growth, insulin sensitivity and glucose tolerance.

Indexed as

Cell SizeEnergy MetabolismSignal TransductionAdipocytesAdiposityAnimalsCells, CulturedChloride ChannelsDisease Models, AnimalForkhead Box Protein O1GlucoseGlucose Transporter Type 4Glycogen Synthase Kinase 3 betaGRB2 Adaptor ProteinHomeostasisHumansAKT2 protein, humanAkt2 protein, mouseChloride ChannelsForkhead Box Protein O1FOXO1 protein, humanFoxo1 protein, mouseGlucoseGlucose Transporter Type 4Glycogen Synthase Kinase 3 betaGRB2 Adaptor ProteinGRB2 protein, humanGrb2 protein, mouseGSK3B protein, humanGsk3b protein, mouseInsulinLRRC8A protein, humanLRRC8A protein, mouseMembrane ProteinsPhosphatidylinositol 3-KinaseProto-Oncogene Proteins c-aktSLC2A4 protein, humanSlc2a4 protein, mouse

Identifiers

PMID28436964
PMCPMC5415409
OpenAlexW2610125817

What OpenQuestion holds

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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.