Evidence map›Paper›PMID 41644943›Full record

ArticleNature communications2026

The focal adhesion kinases regulate leptin action and the weight reducing effect of HDAC6 inhibition.

Colleen K Hadley, Luca Galgano, Yijun Gui, Antonio M Carvalho da Silva, Danielle T Porter, Yanan Wu, Yuanting Lai, Mauro Torti, Işın Çakır

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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

9 authors.

Colleen K Hadley *Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Luca Galgano *Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Yijun Gui *Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-9174-2437
Antonio M Carvalho da Silva *Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-8017-104X
Danielle T PorterLife Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Yanan WuLife Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Yuanting LaiDivision of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Mauro TortiDepartment of Biology and Biotechnology, University of Pavia, Pavia, Italy.
Işın ÇakırLife Sciences Institute, University of Michigan, Ann Arbor, MI, USA. cakiri@pitt.edu.ORCID http://orcid.org/0000-0003-4293-7267

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID P OLSON · 2013 to 2026
$24.3M
Weill Cornell/Rockefeller/Sloan Kettering MST ProgramT32GM152349 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI KATHARINE C HSU · 2024 to 2026
$6.6M
Melanocortin Signaling in Feeding BehaviorR01DK070332 · NIDDK · VANDERBILT UNIVERSITY · PI CONE, ROGER D. · 2004 to 2017
$6.1M
Role of HDAC6 in the Regulation of Energy Homeostasis and Leptin SensitivityR01DK125830 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CONE, ROGER D. · 2021 to 2024
$1.6M
NIDDK NIH HHS P30 DK020572NIDDK NIH HHS R01 DK070332NIDDK NIH HHS R01 DK125830NIGMS NIH HHS T32 GM152349
6 · The paper itself

Abstract

The adipokine leptin is a central regulator of energy metabolism. We previously showed that HDAC6 inhibitors enhance central leptin sensitivity. Using integrative analyses of leptin-responsive hypothalamic gene expression signatures, we identified focal adhesion kinases (FAK and PYK2) as essential for the anorectic effect of leptin and the anti-obesity action of HDAC6 inhibitors in male mice. The effect of tubastatin A, an HDAC6 inhibitor, is compromised in Pyk2 knockout mice, and central inhibition of focal adhesion kinases blocks tubastatin-induced weight loss. Focal adhesion kinases phosphorylate and activate the transcription factor STAT3 downstream of leptin receptor, and leptin signaling is attenuated when these kinases are knocked down or inhibited. Finally, hypothalamic knockdown of focal adhesion kinases blunts leptin action, leads to hyperphagic obesity, and attenuates the anti-obesity effect of HDAC6 inhibitors. These findings suggest that FAK and PYK2 are previously uncharacterized members of the leptin receptor signaling and critical mediators of central leptin sensitization.

Indexed as

Focal Adhesion Kinase 1Focal Adhesion Kinase 2Histone Deacetylase InhibitorsHistone DeacetylasesLeptinWeight LossAnimalsHistone Deacetylase 6Hydroxamic AcidsHypothalamusIndolesMaleMiceMice, Inbred C57BLMice, KnockoutObesityFocal Adhesion Kinase 1Focal Adhesion Kinase 2Hdac6 protein, mouseHistone Deacetylase 6Histone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsIndolesLeptinPtk2b protein, mousePtk2 protein, mouseReceptors, LeptinSTAT3 Transcription Factortubastatin A

Identifiers

PMID41644943
PMCPMC12877105

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.