cGAS/STING and innate brain inflammation following acute high-fat feeding.
Authors Elzinga SE, Henn R, Murdock BJ, Kim B, Hayes JM, Mendelson F, Webber-Davis I,
Teener S, Pacut C, Lentz SI, Feldman EL
Submitted By Submitted Externally on 11/2/2022
Status Published
Journal Frontiers in immunology
Year 2022
Date Published
Volume : Pages 13 : 1012594
PubMed Reference 36248795
Abstract Obesity, prediabetes, and diabetes are growing in prevalence worldwide. These
metabolic disorders are associated with neurodegenerative diseases, particularly
Alzheimer's disease and Alzheimer's disease related dementias. Innate
inflammatory signaling plays a critical role in this association, potentially
via the early activation of the cGAS/STING pathway. To determine acute systemic
metabolic and inflammatory responses and corresponding changes in the brain, we
used a high fat diet fed obese mouse model of prediabetes and cognitive
impairment. We observed acute systemic changes in metabolic and inflammatory
responses, with impaired glucose tolerance, insulin resistance, and alterations
in peripheral immune cell populations. Central inflammatory changes included
microglial activation in a pro-inflammatory environment with cGAS/STING
activation. Blocking gap junctions in neuron-microglial co-cultures
significantly decreased cGAS/STING activation. Collectively these studies
suggest a role for early activation of the innate immune system both
peripherally and centrally with potential inflammatory crosstalk between neurons
and glia.