Evidence map›Paper›PMID 42025169›Full record

ArticleCell metabolism2026

Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein.

Anthony H Tsang, Nicholas Heeley, Constanza Alcaino, Eunsang Hwang, Brian Y Lam, Taufiq Rahman, Tamana Darwish, Danae Nuzzaci, Richard G Kay, Amar Sarkar and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 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

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.

Anthony H TsangInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Nicholas HeeleyInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Constanza AlcainoInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Eunsang HwangDepartment of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Brian Y LamInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Taufiq RahmanDepartment of Pharmacology, University of Cambridge, Cambridge, UK.
Tamana DarwishInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Danae NuzzaciInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Richard G KayInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Amar SarkarInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Ruiyan WangInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Nihal BashaInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Austin PunnooseInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Peter KirwanInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Marcella MaInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Giles S YeoInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Florian T MerkleInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Fiona M GribbleInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Frank ReinmannInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK.
Kevin W WilliamsDepartment of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
Clémence BlouetInstitute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Cambridge, UK. Electronic address: csb69@cam.ac.uk.

Funding

Decoding Bariatric Surgery Outcomes through Activity and Transcriptional Analysis of Melanocortin NeuronsR01DK141541 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI KEVIN W WILLIAMS · 2025 to 2026
$1.6M
Cellular and Synaptic Reorganization after Exercise TrainingR01DK119169 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI WILLIAMS, KEVIN W · 2018 to 2021
$1.6M
Acute and chronic effects of GLP-1R agonism on NPY/AgRP neuronal activityR56DK135501 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI WILLIAMS, KEVIN W · 2024 to 2024
$410k
NIDDK NIH HHS R01 DK119169NIDDK NIH HHS R01 DK141541NIDDK NIH HHS R56 DK135501Wellcome Trust
6 · The paper itself

Abstract

Dietary protein promotes satiety and weight loss, yet how appetite-regulating neurons sense dietary protein remains poorly understood. Here, we show that Cacna1g, which encodes the T-type voltage-gated calcium channel Cav3.1, is enriched in hypothalamic leucine-sensing neurons and mediates neuronal leucine sensing. Pharmacological inhibition of Cav3.1 blunts leucine-induced activation of pro-opiomelanocortin (POMC) neurons in cultured neurons and brain slices, thereby suppressing the anorectic response to hypothalamic leucine in vivo. Genetic deletion of Cacna1g in POMC neurons abolishes the appetite- and weight-suppressive effects of high-protein feeding. Mechanistically, leucine binds a hydrophobic pocket of Cav3.1 and lowers its threshold for voltage-dependent activation. Finally, pharmacological activation of mediobasal hypothalamic Cav3.1 promotes weight loss in diet-induced obese mice and potentiates responses to anorectic agents, including liraglutide. Together, these findings establish hypothalamic Cav3.1 as a neuronal leucine sensor and nominate it as a tractable target for anti-obesity therapy.

Indexed as

Calcium Channels, T-TypeDietary ProteinsLeucineNeuronsWeight LossAnimalsHypothalamusMaleMiceMice, Inbred C57BLMice, KnockoutObesityPro-OpiomelanocortinCalcium Channels, T-TypeDietary ProteinsLeucinePro-Opiomelanocortinappetitearcuate nucleusdietary proteinshypothalamusleucinemetabolic diseasesnutrient sensingobesityPOMC neuronsvoltage-gated calcium channel

Identifiers

PMID42025169
PMCPMC7619568

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.