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Published on: October 17, 2018
Chronic High-Fat Diet Consumption Followed by Lipopolysaccharide Challenge Induces Persistent and Long-Lasting
Titikorn Chunchai1,2, Hiranya Pintana1,2, Chanon Kunasol1,2
1Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Aim:
Microglia exhibit innate immune memory, altering their responses to subsequent challenges. Consumption of high-fat diet (HFD) triggers innate immune responses, but the characteristics of HFD-induced microglial priming remain unclear. We aim to investigate how HFD-induced microglial priming, followed by a lipopolysaccharide (LPS) challenge, affects brain functions.
Methods:
Male Wistar rats were divided into control, unprimed, and primed groups. The primed groups received either a single LPS injection (0.5 mg/kg, intraperitoneally) or HFD consumption for 4-8 weeks. Following the priming phase, all rats (except controls) were subjected to an LPS challenge with a 4- or 8-week interval. After 24 h of LPS challenge, cognition, anxiety-, and depressive-like behaviors were assessed. The brain and hippocampus were collected for further analysis.
Results:
Both LPS- and 4-week HFD-primed groups, followed by LPS challenge, exhibited increased peripheral and brain oxidative stress, impaired neurogenesis, disrupted neurotransmitter balance, and altered glycolysis and Krebs cycle substrates. These changes also caused microglial morphological alterations, elevated C1q levels, and synaptic loss, which were associated with anxiety- and depressive-like behaviors, indicating that 4-week HFD consumption has a similar immune priming ability to a single dose of LPS injection. Extending HFD priming to 8 weeks exacerbated microglial and brain inflammation, synaptic loss, and behavioral deficits. Furthermore, prolonging the interval between priming and LPS challenge worsened inflammation and cognitive decline, suggesting the persistent effects of microglial priming.
Conclusions:
HFD consumption persistently and time-dependently primes microglia similar to a single LPS injection, influencing immune responses and contributing to behavioral abnormalities.
Insights
High-fat diet consumption primes microglia, similar to LPS injection, leading to brain inflammation and behavioral issues. These effects persist and worsen with longer diet duration and shorter intervals before challenge.
Area of Science:
- Neuroscience
- Immunology
- Metabolic Disorders
Background:
- Microglia possess innate immune memory, modifying responses to subsequent stimuli.
- High-fat diet (HFD) consumption activates innate immune responses, but HFD-induced microglial priming is not well understood.
Purpose of the Study:
- To investigate the effects of HFD-induced microglial priming followed by lipopolysaccharide (LPS) challenge on brain function.
- To characterize the nature and duration of HFD-induced microglial priming.
Main Methods:
- Rats were assigned to control, unprimed, or primed groups (LPS injection or HFD for 4-8 weeks).
- Primed rats received an LPS challenge after a 4- or 8-week interval.
- Cognition, behavior, and brain/hippocampal tissues were analyzed post-challenge.
Main Results:
- Both LPS and 4-week HFD priming led to oxidative stress, impaired neurogenesis, altered neurotransmitters, and synaptic loss, causing anxiety- and depressive-like behaviors.
- Extended HFD priming (8 weeks) worsened inflammation, synaptic loss, and behavioral deficits.
- Longer intervals between priming and LPS challenge exacerbated inflammation and cognitive decline, indicating persistent microglial priming.
Conclusions:
- HFD consumption persistently primes microglia in a time-dependent manner, mirroring LPS-induced priming.
- This HFD-induced microglial priming influences immune responses and contributes to behavioral abnormalities.
