Evidence map›Paper›PMID 42127320›Full record

ArticleDiabetes2026

Nicotinic Acetylcholine Receptor Signaling Activates Beige Adipocytes and Mediates Systemic Metabolism.

Shanshan Liu, Kezhou Zhu, Wenwen Zhang, Tong Pan, Martin O'Brien, Ichitaro Abe, Lily Dale, Justin Piejak, Nadia Houssein, Biyang Zhang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Shanshan LiuLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Kezhou ZhuLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Wenwen ZhangLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Tong PanLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Martin O'BrienDivision of Geriatrics and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
Ichitaro AbeDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA.
Lily DaleLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Justin PiejakLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Nadia HousseinLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Biyang ZhangLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Matthew FeinLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Shingo KajimuraDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, and Howard Hughes Medical Institute, Boston, MA.ORCID 0000-0003-0672-5910
Raymond YungDivision of Geriatrics and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
X Z Shawn XuLife Sciences Institute, University of Michigan, Ann Arbor, MI.
Jun WuLife Sciences Institute, University of Michigan, Ann Arbor, MI.ORCID 0000-0003-4493-5820

Funding

Molecular mechanisms of UCP1-independent pathways in metabolic healthR01DK097441 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Shingo Kajimura · 2012 to 2026
$5.9M
The role of immune-adipocyte cholinergic signaling during metabolic adaptation and dysfunctionR01DK107583 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WU, JUN · 2016 to 2024
$3.4M
A novel cholinergic circuitry in alcoholic liver disease (NIAAA)R01AA028761 · NIAAA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WU, JUN · 2021 to 2025
$2.1M
Division of Diabetes, Endocrinology, and Metabolic Diseases R01DK107583Howard Hughes Medical InstituteNIAAA NIH HHS R01 AA028761NIAAA NIH HHS R01AA028761NIDDK NIH HHS R01 DK097441NIDDK NIH HHS R01DK097441NIDDK NIH HHS R01 DK107583
6 · The paper itself

Abstract

Optimal function of beige adipocytes is essential for energy balance and metabolic homeostasis. We previously identified that cholinergic receptor nicotinic α2 subunit (CHRNA2) mediates a beige fat selective signaling in mice and humans. Here, we investigate the molecular composition of CHRNA2-containing nicotinic acetylcholine receptors (nAChRs) in beige adipocytes and its impact on whole-body metabolism. Expression levels of cholinergic receptor nicotinic β2 subunit (CHRNB2) and CHRNA2 positively correlate within murine and human beige adipocytes, and both nAChRs are regulated by a spectrum of beige fat regulators. CHRNB2 is essential for the response to nAChR agonists in beige adipocytes. CHRNB2 partial agonists, a family of drugs clinically used for smoking cessation, activate both murine and human beige adipocytes. Mice deficient in Chrnb2, with both whole-body knockout or adipocyte-specific deletion, exhibit compromised adaptive thermogenesis in subcutaneous fat and more aggravated metabolic dysfunction after challenge with high-fat-diet feeding compared with control mice, underscoring the importance of the nAChR signaling in maintaining energy balance. This cholinergic signaling declines in subcutaneous fat with aging. These findings indicate CHRNB2 forms a functional receptor with CHRNA2 in beige adipocytes and highlight their potential as therapeutic targets against metabolic disorders. ARTICLE HIGHLIGHTS: Beige adipocyte activity, mediated by CHRNA2, significantly influences adipose function and systemic metabolism. The CHRNB2 subunit forms a functional receptor with CHRNA2 and is essential for the response to nicotinic acetylcholine receptor agonists in beige adipocytes. Deletion of Chrnb2 in mice compromises the adaptive response to cold in subcutaneous adipose tissue and renders exacerbated metabolic dysfunction due to diet-induced obesity. This cholinergic signaling within subcutaneous adipose tissue declines with aging. CHRNB2 partial agonists, a family of drugs clinically used for smoking cessation, activate both murine and human beige adipocytes.

Indexed as

Adipocytes, BeigeReceptors, NicotinicAnimalsDiet, High-FatEnergy MetabolismHumansMaleMiceMice, Inbred C57BLMice, KnockoutSignal TransductionThermogenesisCHRNA2 protein, mouseReceptors, Nicotinic

Identifiers

PMID42127320
PMCPMC13493213

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.