Evidence map›Paper›PMID 41636042›Full record

ArticleCirculation research2026

Leptin Activates Brain-BAT-Heart Crosstalk to Promote Cardiac Protection.

Ana C M Omoto, Ivan Vechetti, Jussara M do Carmo, Zhen Wang, Alan J Mouton, John C Young, Xuemei Dai, Emily C Ladnier, Sumaya C Zenum, Odecio E S Tosta and 9 more

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Article in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

  1. Review
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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

19 authors.

Ana C M OmotoDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).ORCID 0000-0003-1062-7109
Ivan VechettiDepartment of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE (I.V.).ORCID 0000-0003-1024-1011
Jussara M do CarmoDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).
Zhen WangDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).ORCID 0000-0002-8028-8942
Alan J MoutonDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).ORCID 0000-0001-5973-3071
John C YoungDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).ORCID 0009-0006-6487-8674
Xuemei DaiDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).
Emily C LadnierDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).
Sumaya C ZenumSchool of Medicine, Centro Universitario Barao de Maua, Ribeirao Preto, SP, Brazil (S.C.Z., O.E.S.T., L.R.).
Odecio E S TostaSchool of Medicine, Centro Universitario Barao de Maua, Ribeirao Preto, SP, Brazil (S.C.Z., O.E.S.T., L.R.).
Luisa RomeiroSchool of Medicine, Centro Universitario Barao de Maua, Ribeirao Preto, SP, Brazil (S.C.Z., O.E.S.T., L.R.).ORCID 0009-0009-6932-1172
Madison HambyDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).
Xuan LiDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).ORCID 0000-0001-5781-1662
Robert W SpitzDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).
Alyssa M RichardsWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN (A.M.R., C.H.J., C.J.G.).
Cortland H JohnsWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN (A.M.R., C.H.J., C.J.G.).ORCID 0009-0009-8876-8906
Craig J GoergenWeldon School of Biomedical Engineering, Purdue University, West Lafayette, IN (A.M.R., C.H.J., C.J.G.).ORCID 0000-0001-8883-7953
Alexandre A da SilvaDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).ORCID 0000-0003-4504-0607
John E HallDepartment of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS (A.C.M.O., J.M.d.C., Z.W., A.J.M., J.C.Y., X.D., E.C.L., M.H., X.L., R.W.S., A.A.d.S., J.E.H.).ORCID 0000-0001-9867-5855

Funding

Training and Mentoring Core P20GM103476 · NIGMS · UNIVERSITY OF SOUTHERN MISSISSIPPI · PI Yufeng Zheng · 2012 to 2026
$60.2M
Tracking and Evaluation CoreU54GM115428 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI JONES, ALAN E · 2016 to 2025
$38.2M
The role of leptin in autoimmune-associated hypertensionP20GM104357 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI TAYLOR, ERIN BASSFORD · 2013 to 2022
$23.4M
Sex differences in operant cocaine memoriesP20GM144041 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI Ramona Moles · 2023 to 2026
$12.1M
Pilot Projects ProgramP30GM149404 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI DAVID E STEC · 2023 to 2026
$6.3M
Cardiac protective mechanisms of melanocortin system activationR01HL163076 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI Jussara M. Do Carmo, Alexandre Alves da Silva · 2023 to 2026
$2.3M
Brain MC4R-BAT-Heart crosstalk: a potential new therapeutic target for myocardial ischemia/reperfusion injuryR01HL181254 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI Ana Carolina Mieko Omoto · 2025 to 2026
$1.1M
Long-term consequences of parental obesity on developmental programming of cardiorenal diseases in offspringR01DK121411 · NIDDK · UNIVERSITY OF MISSISSIPPI MED CTR · PI DO CARMO, JUSSARA M. · 2019 to 2021
$818k
NHLBI NIH HHS R01 HL163076NHLBI NIH HHS R01 HL181254NIDDK NIH HHS R01 DK121411NIGMS NIH HHS P20 GM103476NIGMS NIH HHS P20 GM104357NIGMS NIH HHS P20 GM144041NIGMS NIH HHS P30 GM149404NIGMS NIH HHS U54 GM115428
6 · The paper itself

Abstract

backgroundCardiovascular disease remains the leading cause of death worldwide, with coronary artery disease being the primary contributor. Our recent studies suggest that activation of LepRs (leptin receptors) in the brain can improve cardiac function after myocardial infarction. However, the mechanism by which this cardioprotective effect is transmitted from the brain to the heart remains unclear. We hypothesize that brain LepR activation stimulates brown adipose tissue (BAT) to secrete extracellular vesicles (EVs) enriched with cardioprotective factors. These EVs may safeguard the heart by modulating cardiac mitochondrial function and collagen deposition.

methodsSprague-Dawley rats with BAT intact, BAT ablation, or BAT sympathetic denervation were implanted with an intracerebroventricular cannula for continuous leptin or vehicle delivery over 28 days after cardiac ischemia-reperfusion injury. Cardiac function was assessed weekly via echocardiography and by ventricular catheterization at the end of the protocol. EVs were isolated from BAT for analysis. Rab27a (Ras-related protein Rab-27A), a protein required for EV release, was knocked down using adeno-associated virus, and EV tracking was conducted using a double fluorescent reporter mouse model.

resultsOur findings indicate that BAT ablation or BAT sympathetic denervation diminishes the cardioprotective effects of brain LepR activation. We also observed an increased concentration of EVs within the BAT of rats treated with intracerebroventricular leptin compared with vehicle-treated controls, an effect abolished by BAT denervation. Furthermore, knockdown of Rab27a in BAT reduced the cardioprotective benefits of brain LepR activation. MicroRNA miR-29c-3p was identified as a cargo of leptin-stimulated BAT-derived EVs and appears to play a key role in mitigating cardiac fibrosis after ischemia-reperfusion injury in leptin-treated animals.

conclusionsActivation of LepR in the brain protects the heart after ischemia-reperfusion injury via sympathetic-mediated BAT-derived EVs enriched with miR-29c-3p.

Indexed as

Adipose Tissue, BrownBrainLeptinMyocardial Reperfusion InjuryMyocardiumAnimalsExtracellular VesiclesMaleMiceMyocardial InfarctionRatsRats, Sprague-DawleyReceptors, LeptinLeptinReceptors, Leptinadipose tissue, brownextracellular vesiclesheart failureischemia-reperfusion injurymitochondriamyocardial infarctionsympathetic nervous system

Identifiers

PMID41636042
PMCPMC12875649

What Socratic 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 Socratic graph.