Meta-analysis of the effects of palmitic acid on microglia activation and neurodegeneration

Abstract Objectives Evidence suggests that obesity may represent a risk factor for neurodegenerative pathologies including Alzheimer’s disease (AD). With excessive accumulation of adipose tissue, obesity is associated with chronic low-grade inflammation, increased production of adipokines, elevated levels of free fatty acids (FFAs) including palmitic acid (PA), the most abundant saturated fatty acid (SFA) in circulation. Excessive PA has been shown to induce lipotoxicity in many different types of cells including microglia and neuronal cells. We hypothesized that PA may contribute to the development of obesity-associated neurological conditions. Methods This study was designed to examine how increased PA may affect microglia activation and neurodegeneration using QIAGEN Ingenuity Pathway Analysis (IPA). Kramer analysis was used to quantitatively characterize the impact of PA on microglia activation and neurodegeneration. Results Simulated increase of PA enhanced the activities of intermediating molecules including CCL5, IL1β, IL1RN, IL6, NF-κB, NOS2, PTGS2, TLR2, TLR4, and TNF. Increased PA level induced microglia activation with a z score of 2.38 (p=0.0173) and neurodegeneration with a z score of 1.55 (p=0.121). Increased PA level also activated neuroinflammation signaling pathway, the top canonical pathway associated with both microglia activation and neurodegeneration. Conclusions Our IPA analysis demonstrated that increased PA significantly induced microglia activation and might augment neurodegeneration by altering the activities of key intermediating molecules and canonical pathways. Our findings shed light on how increased PA level may contribute to the development of neurodegenerative pathologies in the course of obesity.