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Cited by 63Fibroblast Growth Factor ResearchRegulation of Appetite and ObesityPancreatic function and diabetes

Hypothalamic perineuronal net assembly is required for sustained diabetes remission induced by fibroblast growth factor 1 in rats

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Alonge, Kimberly M., Mirzadeh, Zaman, Scarlett, Jarrad M., Logsdon, Aric F., Brown, Jenny M., Cabrales, Elaine, Chan, Christina K., Kaiyala, Karl J. +6 more·2020·Nature Metabolism
DOI 10.1038/s42255-020-00275-6PMC PMC7572652
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Abstract

We recently showed that perineuronal nets (PNNs) enmesh glucoregulatory neurons in the arcuate nucleus (Arc) of the mediobasal hypothalamus (MBH)1, but whether these PNNs play a role in either the pathogenesis of type 2 diabetes (T2D) or its treatment remains unclear. Here we show that PNN abundance within the Arc is markedly reduced in the Zucker diabetic fatty (ZDF) rat model of T2D, compared with normoglycaemic rats, correlating with altered PNN-associated sulfation patterns of chondroitin sulfate glycosaminoglycans in the MBH. Each of these PNN-associated changes is reversed following a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) at a dose that induces sustained diabetes remission in male ZDF rats. Combined with previous work localizing this FGF1 effect to the Arc area 2-4, our finding that enzymatic digestion of Arc PNNs markedly shortens the duration of diabetes remission following icv FGF1 injection in these animals identifies these extracellular matrix structures as previously unrecognized participants in the mechanism underlying diabetes remission induced by the central action of FGF1.

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  • Central administration of FGF-1 into rats induces >2x increase in WFA+ PNNs after 24h and significantly increases the relative abundance of the 2S6S-CS isomer.

    “We recently showed that central administration of FGF-1 into rats 1) induces >2x increase in WFA+ PNNs after 24h, and 2) significantly increases the relative abundance of the 2S6S-CS isomer (Alonge et al. 2020).”

    From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Alonge et al. 2020

    The main text and Extended Data Fig. 2 report a significant increase in arcuate PNN fluorescence 24 hours after central FGF1 injection in Wistar rats, but the text provided does not establish the claimed >2-fold magnitude. The main text reports increased Δ2S6S-CS in FGF1-treated ZDF rats, measured 24 days after injection, not at the 24-hour assessment. The Methods describe CS isomers as relative percentages of total CS composition. (LLM, conf=0.87)

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Research works printed but not linked: 36

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Authors
Alonge, K. M., Mirzadeh, Z., Scarlett, J. M., Logsdon, A. F., Brown, J. M., Cabrales, E., Chan, C. K., Kaiyala, K. J., Bentsen, M. A., Banks, W. A., Guttman, M., Wight, T. N., Morton, G. J., & Schwartz, M. W.
Affiliations
  • University of Washington (US)
  • Barrow Neurological Institute (US)
  • Seattle Children's Hospital (US)
  • Benaroya Research Institute (US)
  • University of Copenhagen (DK)
Corresponding author
Schwartz, Michael W.
ORCID
Venue
Nature Metabolism
Publisher
Springer Science and Business Media LLC
Published
2020-09-07
Volume
2
Issue
10
Pages
1025-1033
ISSN
2522-5812 (ISSN-L)
DOI
10.1038/s42255-020-00275-6
PMC
PMC7572652
OpenAlex
W3083691524
Cited by
63
References
6
Citations by year
2026: 6 · 2025: 18 · 2024: 15 · 2023: 4 · 2022: 9 · 2021: 8 · 2020: 3
FWCI
1.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Metabolism (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health & Human Services | National Institutes of Health (F32DK122662, K12NS080223, K08DK114474, T32AG052354, R01GM127579, R01DK089056, P30DK035816, R01DK101997, R01DK083042)
  • UW | Diabetes Research Center, University of Washington (P30DK017047)
  • U.S. Department of Defense (W81XWH-20-1-0250)
  • Barrow Neurological Foundation (18-0025-30-05)
  • Novo Nordisk Fonden (NNF17OC0024328)
  • Novo Nordisk Foundation Center for Basic Metabolic Research (NNF10CC1016515)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
perineuronal nets, fibroblast growth factor 1, type 2 diabetes remission, arcuate nucleus, mediobasal hypothalamus, extracellular matrix remodeling, intracerebroventricular administration, Zucker diabetic fatty rats
MeSH terms
Aged, Animals, Blood Glucose, Body Weight, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Eating, Extracellular Matrix, Humans, Hypothalamus, Injections, Intraventricular, Male, Middle Aged, Neurons, Rats, Zucker, Fibroblast Growth Factor 1, Rats, Wistar, Rats, Young Adult

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