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.

Can Bioimpedance Measurements of Lean and Fat Tissue Mass Replace Subjective Global Assessments in Peritoneal Dialysis Patients?

OBJECTIVE: Malnutrition and protein energy wasting (PEW) determined by Subjective Global Assessment (SGA) is associated with increased mortality. There is an inverse relationship between body mass and overhydration in dialysis patients. Is the predictive accuracy of SGA (for death) independent of hydration status? Can bioimpedance spectroscopy analysis of lean tissue index (LTI) and fat tissue index (FTI) accurately identify dialysis patients with protein energy wasting and increased mortality? METHODS: We report an observational study of 455 peritoneal dialysis (PD) patients. RESULTS: We found that 96 patients (21%) were malnourished (SGA score between 1 and 5), and 192 (42%) had LTI values below 10th centile (age, gender adjusted). FTI was significantly lower in the SGA-defined malnourished cohort. By contrast, there was an inverse relationship between LTI and FTI. Malnourished (by SGA) patients were significantly more overhydrated (P < .0001), but SGA remained highly predictive of survival in multivariate analysis that included hydration status (hazard ratio: 3.12, 95% confidence interval 1.86-5.23, P < .0001). Obesity (patients with the highest 20% FTI) predicted survival (hazard ratio of death was 0.47, 95% confidence interval 0.16-0.85, P < .02) on univariate but not multivariate analysis. CONCLUSIONS: We have confirmed that SGA is an accurate predictor of mortality in PD patients, and its predictive value is independent of the hydration status. Predictive power of SGA was not affected when LTI and FTI were included in multivariate analysis. Patients with low LTI were different from patients with low SGA (associated with high FTI). Sensitivity and specificity of Body Composition Monitor to diagnose patients with low SGA readings were poor (area under the curve for receiver operator characteristics analysis 0.66). The phenomenon of reverse epidemiology (high FTI predicting a survival advantage) was found in our PD cohort.