Evidence map›Paper›PMID 39005380›Full record

ArticlebioRxiv : the preprint server for biology2024

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

M Valdearcos, E R McGrath, S M Brown Mayfield, A Folick, R T Cheang, L Li, T P Bachor, R N Lippert, A W Xu, S K Koliwad

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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

5 · Who and what money

Authors and funding

10 authors.

M ValdearcosDiabetes Center, University of California, San Francisco, CA, USA.ORCID 0000-0002-5784-2458
E R McGrathDiabetes Center, University of California, San Francisco, CA, USA.
S M Brown MayfieldDiabetes Center, University of California, San Francisco, CA, USA.
A FolickDiabetes Center, University of California, San Francisco, CA, USA.
R T CheangDiabetes Center, University of California, San Francisco, CA, USA.
L LiDiabetes Center, University of California, San Francisco, CA, USA.
T P BachorDiabetes Center, University of California, San Francisco, CA, USA.
R 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.
A W XuDiabetes Center, University of California, San Francisco, CA, USA.
S K KoliwadDiabetes Center, University of California, San Francisco, CA, USA.

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
The role of gut microbiota in regulating functional diversity of diet-responsive hypothalamic myeloid cellsR03DK125627 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VALDEARCOS, MARTIN · 2020 to 2021
$242k
NIDDK NIH HHS K01 DK113064NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK098722NIDDK NIH HHS R01 DK103175NIDDK NIH HHS R01 DK134782NIDDK NIH HHS R03 DK125627
6 · The paper itself

Abstract

Mammalian glucose homeostasis is, in part, nutritionally programmed during early neonatal life, a critical window for the formation of synapses between hypothalamic glucoregulatory centers. Although microglia are known to prune synapses throughout the brain, their specific role in refining hypothalamic glucoregulatory circuits remains unknown. Here, we show that microglia in the mediobasal hypothalamus (MBH) of mice actively engage in synaptic pruning during early life. Microglial phagocytic activity is induced following birth, regresses upon weaning from maternal milk, and is exacerbated by feeding dams a high-fat diet while lactating. In particular, we show that microglia refine perineuronal nets (PNNs) within the neonatal MBH. Indeed, transiently depleting microglia before weaning (P6-16), but not afterward (P21-31), remarkably increased PNN abundance in the MBH. Furthermore, mice lacking microglia only from P6-16 had glucose intolerance due to impaired glucose-responsive pancreatic insulin secretion in adulthood, a phenotype not seen if microglial depletion occurred after weaning. Viral retrograde tracing revealed that this impairment is linked to a reduction in the number of neurons in specific hypothalamic glucoregulatory centers that synaptically connect to the pancreatic β-cell compartment. These findings show that microglia facilitate synaptic plasticity in the MBH during early life through a process that includes PNN refinement, to establish hypothalamic circuits that regulate adult glucose homeostasis.

Identifiers

PMID39005380
PMCPMC11244970

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.