Evidence map›Paper›PMID 42082152›Full record

ArticleMolecular metabolism2026

Increased leptin signaling drives the response of hypothalamic LepRb neurons to diet-induced obesity.

James Dell'Orco, Warren Pan, Margaret B Allison, Abigail J Tomlinson, Jordan Wean, Paul V Sabatini, Christopher J Rhodes, David P Olson, Martin G Myers, Paulette B Goforth

Abstract read
PubMed Full text at PMC Publisher
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.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

James Dell'OrcoDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA.
Warren PanDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA.
Margaret B AllisonDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
Abigail J TomlinsonDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Jordan WeanDepartment of Surgery, University of Michigan, Ann Arbor, MI, USA.
Paul V SabatiniDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Christopher J RhodesDepartment of Medicine, University of Chicago, Chicago, IL, USA.
David P OlsonDivision of Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Martin G MyersDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Graduate Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. Electronic address: mgmyers@umich.edu.
Paulette B GoforthDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, USA. Electronic address: pgoforth@umich.edu.

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

The failure of hyperleptinemia to decrease adiposity in common forms of obesity has led to the notion that impaired leptin receptor (LepRb) signaling ("leptin resistance") might cause obesity. Because LepRb transcriptional signaling plays a central role in leptin action, we defined the control of gene expression in hypothalamic LepRb neurons in diet-induced obese (DIO) mice and in response to changes in circulating leptin. We found that LepRb neurons from DIO mice exhibited transcriptional changes similar to those induced by exogenous leptin. We also examined electrical activity in LepRb neurons from DIO mice, focusing on LepRb neurons in the ventromedial hypothalamic nucleus (VMN). This analysis revealed larger membrane depolarizations in response to current injection for VMN LepRb neurons from DIO mice. This effect was recapitulated by hyperleptinemia in vivo or exposure to elevated leptin ex vivo. Hence, hypothalamic LepRb neurons exhibit increased cellular leptin responses due to hyperleptinemia in DIO animals. These findings contradict the notion that impaired cellular leptin action underlies the development of DIO but rather suggest that increased leptin action drives DIO-associated changes in hypothalamic LepRb neuron function.

Indexed as

HypothalamusLeptinNeuronsObesityReceptors, LeptinAnimalsDiet, High-FatMaleMiceMice, Inbred C57BLSignal TransductionVentromedial Hypothalamic NucleusLeptinleptin receptor, mouseReceptors, LeptinGene expressionHypothalamusLeptinNeuron excitabilityObesity

Identifiers

PMID42082152
PMCPMC13206730

What Socratic holds

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LicenceCC BY
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 Socratic graph.