Evidence map›Paper›PMID 42297286›Full record

ArticleMolecular metabolism2026

Copper import via CTR1 supports the β3-Adrenergic thermogenic program.

Tae-Il Jeon, Young-Seung Lee, Tamara Korolnek, Juyoung Kim, Pratibha Poudel, Parama Bhattacharjee, Xuewei Zhao, Evan Ying, Naili Liu, Tong Xiao and 3 more

Abstract read
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In one paragraph

Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Tae-Il JeonDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD, USA; Department of Animal Science, Chonnam National University, Gwangju, Republic of Korea. Electronic address: tjeon@jnu.ac.kr.
Young-Seung LeeDepartment of Animal Science, Chonnam National University, Gwangju, Republic of Korea.
Tamara KorolnekDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.
Juyoung KimDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.
Pratibha PoudelDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.
Parama BhattacharjeeDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.
Xuewei ZhaoDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.
Evan YingDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD, USA.
Naili LiuMouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
Tong XiaoDepartment of Chemistry, Princeton University, Princeton, NJ, USA.
Christopher J ChangDepartment of Chemistry, Princeton University, Princeton, NJ, USA.
Oksana GavrilovaMouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
Byung-Eun KimDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD, USA; Biological Sciences Graduate Program, University of Maryland, College Park, MD, USA. Electronic address: bekim@umd.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Adaptive thermogenesis requires coordinated activation of mitochondrial oxidation and metabolic remodeling, yet the signals driving this coordination are incompletely understood. Here, we show that cold exposure and β3-adrenergic receptor (β3-AR) stimulation upregulate the high-affinity copper (Cu) importer CTR1 and promote Cu accumulation in thermogenic adipose tissues. Adipocyte-specific Ctr1 knockout (ACKO) mice exhibit markedly reduced energy expenditure and develop severe hypothermia during acute cold challenge. Proteomic analysis of brown adipose tissue (BAT) from ACKO mice reveals coordinated suppression of oxidative phosphorylation and thermogenic metabolic programs, accompanied by attenuation of lipolytic pathways. Cu deficiency also impairs cold- and β3-AR-induced lipolytic activation, including reduced HSL phosphorylation and lipid clearance in both BAT and inguinal white adipose tissue (iWAT). Although BAT-specific Ctr1 deletion (BCKO) leaves acute β3-adrenergic responses largely intact, these mice still exhibit cold intolerance, indicating that BAT Cu homeostasis is critical for sustaining thermogenic capacity during cold challenge. Treatment with the Cu ionophore elesclomol partially restores mitochondrial oxidative capacity and improves cold tolerance in ACKO mice. Together, these findings identify CTR1-dependent Cu import as an inducible component of the β3-adrenergic thermogenic program and establish intracellular Cu availability as a key determinant of thermogenic capacity during adaptive thermogenesis.

Indexed as

CopperCopper Transporter 1Receptors, Adrenergic, beta-3ThermogenesisAdipocytesAdipose Tissue, BrownAdipose Tissue, WhiteAnimalsCold TemperatureEnergy MetabolismMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaCopperCopper Transporter 1Receptors, Adrenergic, beta-3Slc31a1 protein, mouseAdaptive thermogenesisBrown adipose TissueCopper homeostasisCTR1β3-Adrenergic signaling

Identifiers

PMID42297286
PMCPMC13324307

What Socratic 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 Socratic graph.