Evidence map›Paper›PMID 33248294›Full record

ArticleMolecular metabolism2021

Adaptive thermogenesis in brown adipose tissue involves activation of pannexin-1 channels.

Subramanian Senthivinayagam, Vlad Serbulea, Clint M Upchurch, Renata Polanowska-Grabowska, Suresh K Mendu, Srabani Sahu, Prathiba Jayaguru, Kevin W Aylor, Mahendra D Chordia, Limor Steinberg and 11 more

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 34 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

21 authors at 5 institutions in 2 countries.

Subramanian SenthivinayagamDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Vlad SerbuleaDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Clint M UpchurchDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Renata Polanowska-GrabowskaDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Suresh K MenduDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Srabani SahuDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Prathiba JayaguruDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Kevin W AylorDivision of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Mahendra D ChordiaDepartment of Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Limor SteinbergDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Nathaniel OberholtzerDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Seichii UchiyamaGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Noriko InadaGraduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Ulrike M LorenzDepartment of Microbiology, Immunology and Cancer Biology, Center for Cell Clearance, the Beirne B. Carter Center for Immunology Research, USA.
Thurl E HarrisDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Susanna R KellerDivision of Endocrinology and Metabolism, Department of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Akshaya K MeherDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Alexandra KadlDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Bimal N DesaiDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Bijoy K KunduDepartment of Radiology and Medical Imaging, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA; Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA.
Norbert LeitingerDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, 22908, USA; Robert M Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA. Electronic address: nl2q@virginia.edu.
University of Virginia · USCarter Center · USOsaka Prefecture University · JPThe University of Tokyo · JPUniversity of Virginia Medical Center · US

Funding

Role of Pannexins in Vascular Smooth Muscle CellsP01HL120840 · NHLBI · UNIVERSITY OF VIRGINIA · PI BAYLISS, DOUGLAS A. · 2014 to 2023
$24.0M
TRAINING IN THE PHARMACOLOGICAL SCIENCEST32GM007055 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LYNCH, KEVIN R. · 1985 to 2022
$7.2M
Myocardial Metabolic Remodeling in Cardiac HypertrophyR01HL123627 · NHLBI · UNIVERSITY OF VIRGINIA · PI KUNDU, BIJOY K · 2015 to 2018
$1.9M
Role of Oxidized neutral lipids in adipocyte functionR01DK101946 · NIDDK · UNIVERSITY OF VIRGINIA · PI HARRIS, THURL E. · 2014 to 2018
$1.7M
The Role of Oxidized Phospholipids in Macrophage Bioenergetics and InflammationF31DK108553 · NIDDK · UNIVERSITY OF VIRGINIA · PI SERBULEA, VLAD · 2016 to 2017
$60k
NHLBI NIH HHS P01 HL120840NHLBI NIH HHS R01 HL123627NIDDK NIH HHS F31 DK108553NIDDK NIH HHS R01 DK101946NIGMS NIH HHS T32 GM007055
6 · The paper itself

Abstract

objectiveBrown adipose tissue (BAT) is specialized in thermogenesis. The conversion of energy into heat in brown adipocytes proceeds via stimulation of β-adrenergic receptor (βAR)-dependent signaling and activation of mitochondrial uncoupling protein 1 (UCP1). We have previously demonstrated a functional role for pannexin-1 (Panx1) channels in white adipose tissue; however, it is not known whether Panx1 channels play a role in the regulation of brown adipocyte function. Here, we tested the hypothesis that Panx1 channels are involved in brown adipocyte activation and thermogenesis.

methodsIn an immortalized brown pre-adipocytes cell line, Panx1 currents were measured using patch-clamp electrophysiology. Flow cytometry was used for assessment of dye uptake and luminescence assays for adenosine triphosphate (ATP) release, and cellular temperature measurement was performed using a ratiometric fluorescence thermometer. We used RNA interference and expression plasmids to manipulate expression of wild-type and mutant Panx1. We used previously described adipocyte-specific Panx1 knockout mice (Panx1

resultsIn brown adipocytes, Panx1 channel activity was induced either by apoptosis-dependent caspase activation or by β3AR stimulation via a novel mechanism that involves Gβγ subunit binding to Panx1. Inactivation of Panx1 channels in cultured brown adipocytes resulted in inhibition of β3AR-induced lipolysis, UCP-1 expression, and cellular thermogenesis. In mice, adiponectin-Cre-dependent genetic deletion of Panx1 in all adipose tissue depots resulted in defective β3AR agonist- or cold-induced thermogenesis in BAT and suppressed beigeing of white adipose tissue. UCP1-Cre-dependent Panx1 deletion specifically in brown adipocytes reduced the capacity for adaptive thermogenesis without affecting beigeing of white adipose tissue and aggravated diet-induced obesity and insulin resistance.

conclusionsThese data demonstrate that Gβγ-dependent Panx1 channel activation is involved in β3AR-induced thermogenic regulation in brown adipocytes. Identification of Panx1 channels in BAT as novel thermo-regulatory elements downstream of β3AR activation may have therapeutic implications.

Indexed as

Adipocytes, BrownAdiponectinAdipose Tissue, BrownAdipose Tissue, WhiteAnimalsCold TemperatureConnexinsFluorodeoxyglucose F18Insulin ResistanceLipolysisMiceMice, KnockoutNerve Tissue ProteinsObesitySignal TransductionThermogenesisAdiponectinConnexinsFluorodeoxyglucose F18Nerve Tissue ProteinsPanx1 protein, mouseadipocytebrown adipose tissuePannexin channelsThermogenesis

Identifiers

PMID33248294
PMCPMC7779784
OpenAlexW3106631681

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.