High-fat diet feeding differentially affects the development of inflammation in the central nervous system

Abstract

BackgroundObesity and its associated disorders are becoming a major health issue in many countries. The resulting low-grade inflammation not only affects the periphery but also the central nervous system. We set out to study, in a time-dependent manner, the effects of a high-fat diet on different regions of the central nervous system with regard to the inflammatory tone.MethodsWe used a diet-induced obesity model and compared at several time-points (1, 2, 4, 6, 8, and 16 weeks) a group of mice fed a high-fat diet with its respective control group fed a standard diet. We also performed a large-scale analysis of lipids in the central nervous system using HPLC-MS, and we then tested the lipids of interest on a primary co-culture of astrocytes and microglial cells.ResultsWe measured an increase in the inflammatory tone in the cerebellum at the different time-points. However, at week 16, we evidenced that the inflammatory tone displayed significant differences in two different regions of the central nervous system, specifically an increase in the cerebellum and no modification in the cortex for high-fat diet mice when compared with chow-fed mice. Our results clearly suggest region-dependent as well as time-dependent adaptations of the central nervous system to the high-fat diet. The differences in inflammatory tone between the two regions considered seem to involve astrocytes but not microglial cells. Furthermore, a large-scale lipid screening coupled to ex vivo testing enabled us to identify three classes of lipids—phosphatidylinositols, phosphatidylethanolamines, and lysophosphatidylcholines—as well as palmitoylethanolamide, as potentially responsible for the difference in inflammatory tone.ConclusionsThis study demonstrates that the inflammatory tone induced by a high-fat diet does not similarly affect distinct regions of the central nervous system. Moreover, the lipids identified and tested ex vivo showed interesting anti-inflammatory properties and could be further studied to better characterize their activity and their role in controlling inflammation in the central nervous system.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0666-8) contains supplementary material, which is available to authorized users.

Fat food exacerbates post-prandial hypothalamic inflammation involving GFAP+ cells and microglia

“…Given the lack of a peripheral inflammatory response in HFD-fed mice, we subsequently investigated the impact of a HFD on hypothalamic inflammatory markers. Consistent with previous studies (Andre et al, 2017; Baufeld et al, 2016; Buckman et al, 2015; Gao et al, 2017; Gao et al, 2014; Guillemot-Legris et al, 2016; Nadjar et al, 2017; Thaler and Schwartz, 2010; Thaler et al, 2012; Valdearcos et al, 2017; Valdearcos et al, 2014) we found that gene expression of the pro-inflammatory cytokine genes IL1β, IL6 and TNFα, as well as chemokine genes CCL2 and CCL5 was significantly increased in HFD-fed mice compared to SD-fed mice (Fig. 2A-E).…”

“…Since 2012, several studies have shown that HFD consumption induces astrogliosis and microgliosis in the arcuate nucleus (ARC) of the HT (Andre et al, 2017; Balland and Cowley, 2017; Baufeld et al, 2016; Gao et al, 2014; Guillemot-Legris et al, 2016; Kim et al, 2019; Thaler et al, 2012; Valdearcos et al, 2017; Valdearcos et al, 2014). The microglia activation that is induced by lipids and connects dietary fat and brain inflammatory signaling is begging to be seen as the missing link between the hypothalamic response to HFD and susceptibility to obesity (Andre et al, 2017; Kim et al, 2019; Valdearcos et al, 2017; Valdearcos et al, 2014).…”

A2A Adenosine Receptor Antagonism Reverts the Blood-Brain Barrier Dysfunction Induced by Sleep Restriction

“…Here, we again suggest that other mechanisms, independent of adenosine may be participating, such as blood-brain barrier regulation by pro-inflammatory cytokines (as hypothesized in [33]). Indeed it has been shown that the cerebellum seems to be prone to high-fat diet induced neuroinflammation mediated by the endogenous synthesis of the inflammatory mediators monocyte chemo attractant protein-1 (MCP-1), interleukin 1β (IL-1β), tumor necrosis factor-α (TNFα), and cyclooxygenase-2 (COX-2) as compared to the cerebral cortex [36]. In the case of the infection with the attenuated rabies virus CVS-F3 it has been shown that increased cerebellar blood-brain barrier permeability is accompanied by increased local synthesis of TNFα, interferon γ (IFNγ), and intercellular adhesion molecule-1 (ICAM-1) and occurs earlier in the cerebellum than in the cerebral cortex [37].…”

The endogenous bioactive lipid prostaglandin D 2 ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

“…cDNA was synthesized from 1 mg of total RNA using the GoScript Reverse Transcription System (Promega, Madison, WI, USA). qPCR was performed in duplicate for each sample using a SYBR Green mix (GoTaq qPCR Master Mix; Promega) with a STEP one PLUS instrument and software (Applied Biosystems, Foster City, CA, USA) as previously described (26). Products were analyzed by performing a melting curve at the end of the PCR reaction.…”