Evidence map›Paper›PMID 40085644›Full record

ArticleCell reports2025

Microglia mediate the early-life programming of adult glucose control.

Martin Valdearcos, Emily R McGrath, Stephen M Brown Mayfield, Melissa G Jacuinde, Andrew Folick, Rachel T Cheang, Ruoyu Li, Tomas P Bachor, Rachel N Lippert, Allison W Xu and 1 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Critical Periods and Beyond: Dynamic Functions of Perineuronal Nets in Cognition, Development, and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Martin ValdearcosDiabetes Center, University of California, San Francisco, San Francisco, CA, USA. Electronic address: martin.valdearcos@ucsf.edu.
Emily R McGrathDiabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Stephen M Brown MayfieldDiabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Melissa G JacuindeDiabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Andrew FolickDiabetes Center, University of California, San Francisco, San Francisco, CA, USA; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Rachel T CheangDiabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Ruoyu LiDiabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Tomas P BachorDiabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Rachel N LippertGerman Institute of Human Nutrition Potsdam Rehbrücke, Potsdam, Germany; German Center for Diabetes Research, Neuherberg, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany.
Allison W XuDiabetes Center, University of California, San Francisco, San Francisco, CA, USA.
Suneil K KoliwadDiabetes Center, University of California, San Francisco, San Francisco, CA, USA; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. Electronic address: suneil.koliwad@ucsf.edu.

Funding

Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI John Michael Stafford · 2012 to 2026
$29.3M
UCSF Nutrition Obesity Research CenterP30DK098722 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHRISTIAN VAISSE · 2015 to 2026
$14.6M
Microglia: dietary fat-sensitive mediators of inflammation and metabolic diseaseR01DK103175 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOLIWAD, SUNEIL KRISHNA · 2015 to 2019
$1.8M
The microbiota-microglia axis in the regulation of metabolic homeostasisR01DK134782 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Martin Valdearcos · 2023 to 2026
$1.6M
Microglia: Diet-Sensitive Mediators Between Immunity and Hypothalamic FunctionK01DK113064 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VALDEARCOS, MARTIN · 2018 to 2020
$461k
NIDDK NIH HHS K01 DK113064NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK098722NIDDK NIH HHS R01 DK103175NIDDK NIH HHS R01 DK134782
6 · The paper itself

Abstract

Glucose homeostasis is, in part, nutritionally programmed during early neonatal life, a critical window for synapse formation between hypothalamic glucoregulatory centers. Although microglia prune synapses throughout the brain, their role in refining hypothalamic glucoregulatory circuits remains unclear. Here, we show that the phagocytic activity of microglia in the mediobasal hypothalamus (MBH) is induced following birth, regresses upon weaning from maternal milk, and is exacerbated by feeding dams a high-fat diet while lactating. In addition to actively engulfing synapses, microglia are critical for refining perineuronal nets (PNNs) within the neonatal MBH. Remarkably, transiently depleting microglia before weaning (postnatal day [P]6-16) but not afterward (P21-31) induces glucose intolerance in adulthood due to impaired insulin responsiveness, which we link to PNN overabundance and reduced synaptic connectivity between hypothalamic glucoregulatory neurons and the pancreatic β cell compartment. Thus, microglia facilitate early-life synaptic plasticity in the MBH, including PNN refinement, to program hypothalamic circuits regulating adult glucose homeostasis.

Indexed as

GlucoseMicrogliaAnimalsAnimals, NewbornDiet, High-FatFemaleHomeostasisHypothalamusInsulinMaleMiceMice, Inbred C57BLNeuronal PlasticityNeuronsPhagocytosisSynapsesGlucoseInsulinCP: MetabolismCP: Neuroscienceglucose homeostasishypothalamusinsulinmetabolic programmingmicroglianeonatalperineuronal netssynaptic plasticity

Identifiers

PMID40085644
PMCPMC12103245

What OpenQuestion holds

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LicenceCC BY-NC
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.