Unwrapping the mechanisms of ceramide and fatty acid-initiated signals leading to immune-inflammatory responses in obesity.

Abstract

Obesity is considered a global epidemic developed in part as a consequence of the overconsumption of high fat diets. One of the main negative outcomes of obesity is the development of low-grade chronic systemic inflammation, induced by dysregulated immune responses, which can lead to multiple obesity-related diseases. Ceramides are a group of bioactive lipids known to be elevated in obesity and obesity-associated conditions, including cardiovascular disease and type II diabetes. Ceramides may be key players in promoting an obesity-induced inflammatory environment due to their ability to activate key pathways such as Toll-like receptor 4 (TLR4) and NLR pyrin domain containing receptor 3 (Nlrp3), while studies have shown that inhibition of ceramide synthesis gives rise to an anti-inflammatory environment. N-3 polyunsaturated fatty acids (n-3 PUFA) have been of interest due to their anti-inflammatory actions and shown to have beneficial effects in obesity-related diseases. This review will highlight the impact of ceramides in promoting an obesity-induced inflammatory microenvironment and discuss how n-3 PUFA could potentially counteract these responses and have a regulatory effect promoting immune homeostasis.