Exposure to the saturated free fatty acid palmitate alters microglia inflammatory response

Tracy, Linda; Bergqvist, Filip; Ivanova, Elena V.; Jacobsen, Kristin; Iverfeldt, Kerstin

doi:10.1186/1750-1326-8-s1-p42

Cited by 1 publication

(2 citation statements)

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“…Our findings also extend work done in primary astrocytes, in which DHA pretreatment mitigated PA-induced cytokine release (Gupta et al, 2012). In addition to triggering inflammatory responses in the brain, excess accumulation of PA and other SFAs can impair other aspects of cellular function (Tracy et al, 2013;Urso and Zhou, 2021). Thus, we demonstrated that PA treatment dysregulated BV2 microglial expression of several genes associated with ER stress (Chop), mitochondrial homeostasis (Pink1 and Mul1), and autophagy (Atg12) and that DHA pretreatment completely prevented (in the case of Pink1 and Mul1) or partially attenuated (Atg12) this dysregulation.…”

Section: Discussionsupporting

confidence: 82%

“…Importantly, very little work has investigated the impact of PA and other SFAs on microglial phagocytosis. One study utilizing BV2 cells showed that a similar dose (125 µM) of PA potentiated LPSinduced phagocytosis, but did not have an effect on its own (Tracy et al, 2013). In primary microglia, treatment with 100 µM and 200 µM PA inhibited IFNγ-stimulated phagocytosis, but PA alone had no impact (Yanguas-Casás et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Dietary fatty acids differentially impact phagocytosis, inflammatory gene expression, and mitochondrial respiration in microglial and neuronal cell models

Butler,

Mackey-Alfonso,

Massa

et al. 2023

Front. Cell. Neurosci.

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The consumption of diets high in saturated fatty acids and/or refined carbohydrates are associated with neuroinflammation, cognitive dysfunction, and neurodegenerative disease. In contrast, diets high in polyunsaturated fatty acids are associated with anti-inflammatory and neuroprotective effects. We have previously shown that high fat diet (HFD) consumption increases saturated fatty acids and decreases polyunsaturated fatty acids in the hippocampus. We have further shown that HFD elicits exaggerated neuroinflammation and reduced synaptic elements, and results in robust memory deficits in aged rats. Here, we examined the impact of palmitate, an abundant dietary saturated fat, on a variety of cellular responses in BV2 microglia and HippoE-14 neurons, and the extent to which the omega-3 fatty acid, docosahexaenoic acid (DHA), would buffer against these responses. Our data demonstrate that DHA pretreatment prevents or partially attenuates palmitate-induced alterations in proinflammatory, endoplasmic reticulum stress, and mitochondrial damage-associated gene expression in both cell types. Furthermore, we show that synaptoneurosomes isolated from aged, HFD-fed mice are engulfed by BV2 microglia at a faster rate than synaptoneurosomes isolated from aged, chow-fed mice, suggesting HFD alters signaling at synapses to hasten their engulfment by microglia. Consistent with this notion, we found modest increases in complement proteins and a decrease in CD47 protein expression on synaptoneurosomes isolated from the hippocampus of aged, HFD-fed mice. Interestingly, palmitate reduced BV2 microglial phagocytosis, but only of synaptoneurosomes isolated from chow-fed mice, an effect that was prevented by DHA pretreatment. Lastly, we measured the impact of palmitate and DHA on mitochondrial function in both microglial and neuronal cell models using the Seahorse XFe96 Analyzer. These data indicate that DHA pretreatment does not mitigate palmitate-induced reductions in mitochondrial respiration in BV2 microglia and HippoE-14 neurons, suggesting DHA may be acting downstream of mitochondrial function to exert its protective effects. Together, this study provides evidence that DHA can ameliorate the negative impact of palmitate on a variety of cellular functions in microglia- and neuron-like cells.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%