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Citations to this article

Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1+ cells
De-Huang Guo, … , Babak Baban, Alexis M. Stranahan
De-Huang Guo, … , Babak Baban, Alexis M. Stranahan
Published January 14, 2020
Citation Information: J Clin Invest. 2020;130(4):1961-1976. https://doi.org/10.1172/JCI126078.
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Research Article Immunology Neuroscience Article has an altmetric score of 100

Visceral adipose NLRP3 impairs cognition in obesity via IL-1R1 on CX3CR1+ cells

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Abstract

Induction of the inflammasome protein cryopyrin (NLRP3) in visceral adipose tissue (VAT) promotes release of the proinflammatory cytokine IL-1β in obesity. Although this mechanism contributes to peripheral metabolic dysfunction, effects on the brain remain unexplored. We investigated whether visceral adipose NLRP3 impairs cognition by activating microglial IL-1 receptor 1 (IL-1R1). After observing protection against obesity-induced neuroinflammation and cognitive impairment in NLRP3-KO mice, we transplanted VAT from obese WT or NLRP3-KO donors into lean recipient mice. Transplantation of VAT from a WT donor (TRANSWT) increased hippocampal IL-1β and impaired cognition, but VAT transplants from comparably obese NLRP3-KO donors (TRANSKO) had no effect. Visceral adipose NLRP3 was required for deficits in long-term potentiation (LTP) in transplant recipients, and LTP impairment in TRANSWT mice was IL-1 dependent. Flow cytometric and gene expression analyses revealed that VAT transplantation recapitulated the effects of obesity on microglial activation and IL-1β gene expression, and visualization of hippocampal microglia revealed similar effects in vivo. Inducible ablation of IL-1R1 in CX3CR1-expressing cells eliminated cognitive impairment in mice with dietary obesity and in transplant recipients and restored immunoquiescence in hippocampal microglia. These results indicate that visceral adipose NLRP3 impairs memory via IL-1–mediated microglial activation and suggest that NLRP3/IL-1β signaling may underlie correlations between visceral adiposity and cognitive impairment in humans.

Authors

De-Huang Guo, Masaki Yamamoto, Caterina M. Hernandez, Hesam Khodadadi, Babak Baban, Alexis M. Stranahan

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 Total
Citations: 3 16 10 13 10 5 57
Citation information
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Citations to this article in year 2023 (10)

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Association of Obesity With Cognitive Decline in Black and White Americans
Quaye E, Galecki AT, Tilton N, Whitney R, Briceño EM, Elkind MS, Fitzpatrick AL, Gottesman RF, Griswold M, Gross AL, Heckbert SR, Hughes TM, Longstreth WT Jr, Sacco RL, Sidney S, Windham BG, Yaffe K, Levine DA
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Obesity-Induced Brain Neuroinflammatory and Mitochondrial Changes
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Single-cell RNA sequencing identifies hippocampal microglial dysregulation in diet-induced obesity
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iScience 2023
The diverse roles of macrophages in metabolic inflammation and its resolution
Guha Ray A, Odum OP, Wiseman D, Weinstock A
Frontiers in Cell and Developmental Biology 2023
Oxidative stress: The nexus of obesity and cognitive dysfunction in diabetes
Li H, Ren J, Li Y, Wu Q, Wei J
Frontiers in Endocrinology 2023
Pathophysiological Links Between Obesity and Dementia.
Wong Zhang DE, Tran V, Vinh A, Dinh QN, Drummond GR, Sobey CG, Jelinic M, De Silva TM
NeuroMolecular Medicine 2023
Central and Peripheral Inflammation: A Common Factor Causing Addictive and Neurological Disorders and Aging-Related Pathologies
Escobar AP, Bonansco C, Cruz G, Dagnino-Subiabre A, Fuenzalida M, Negrón I, Sotomayor-Zárate R, Martínez-Pinto J, Jorquera G
International journal of molecular sciences 2023
Interaction of high-fat diet and brain trauma alters adipose tissue macrophages and brain microglia associated with exacerbated cognitive dysfunction
Henry RJ, Barrett JP, Vaida M, Khan NZ, Makarevich O, Ritzel RM, Faden AI, Stoica BA
2023
Adipose tissue coregulates cognitive function
Oliveras-Cañellas N, Castells-Nobau A, de la Vega-Correa L, Latorre-Luque J, Motger-Albertí A, Arnoriaga-Rodriguez M, Garre-Olmo J, Zapata-Tona C, Coll-Martínez C, Ramió-Torrentà L, Moreno-Navarrete JM, Puig J, Villarroya F, Ramos R, Casadó-Anguera V, Martín-García E, Maldonado R, Mayneris-Perxachs J, Fernández-Real JM
Science Advances 2023
Region-specific targeting of microglia in vivo using direct delivery of tamoxifen metabolites via microfluidic polymer fibers
Stranahan AM, Tabet A, Anikeeva P
Brain, Behavior, and Immunity 2023

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