Palmitic Acid and Oleic Acid Differently Modulate TLR2-Mediated Inflammatory Responses in Microglia and Macrophages

The relationship between systemic immunity and neuroinflammation is widely recognised. Infiltration of peripheral immune cells to the CNS during certain chronic inflammatory states contributes significantly to neuropathology. Obesity and its co-morbidities are primary risk factors for neuroinflammatory and neurodegenerative conditions, including Alzheimer's disease (AD). Dietary fats are among the most proinflammatory components of the obesogenic diet and play a prominent role in the low-grade systemic inflammation associated with the obese state. Saturated fatty acid (SFA) is largely implicated in the negative consequences of obesity, while the health benefits of monounsaturated fatty acid (MUFA) are widely acknowledged. The current study sought to explore whether SFA and MUFA differently modulate inflammatory responses in the brain, compared with peripheral immune cells. Moreover, we assessed the neuroinflammatory impact of high-fat-induced obesity and hypothesised that a MUFA-rich diet might mitigate inflammation despite obesogenic conditions. Toll-like receptor (TLR)2 mediates the inflammation associated with both obesity and AD. Using the TLR2 agonist lipoteichoic acid (LTA), we report that pre-exposure to either palmitic acid (PA) or oleic acid (OA) attenuated cytokine secretion from microglia, but heightened sensitivity to nitric oxide (NO) production. The reduction in cytokine secretion was mirrored in LTA-stimulated macrophages following exposure to PA only, while effects on NO were restricted to OA, highlighting important cell-specific differences. An obesogenic diet over 12 weeks did not induce prominent inflammatory changes in either cortex or hippocampus, irrespective of fat composition. However, we reveal a clear disparity in the effects of MUFA under obesogenic and non-obesogenic conditions.

Automated summary

The relationship between obesity, neuroinflammation, and neurodegenerative diseases is well recognized. Dietary fats, specifically saturated fatty acids and monounsaturated fatty acids, have different effects on inflammatory responses in the brain. Monounsaturated fatty acids may mitigate inflammation under obesogenic conditions.