Inflammaging and fatty acid oxidation in monocytes and macrophages

Abstract

Fatty acid oxidation (FAO), primarily known as β-oxidation, plays a crucial role in breaking down fatty acids within mitochondria and peroxisomes to produce cellular energy and preventing metabolic dysfunction. Myeloid cells, including macrophages, microglia, and monocytes, rely on FAO to perform essential cellular functions and uphold tissue homeostasis. As individuals age, these cells show signs of inflammaging, a condition that includes a chronic onset of low-grade inflammation and a decline in metabolic function. These lead to changes in fatty acid metabolism and a decline in FAO pathways. Recent studies have shed light on metabolic shifts occurring in macrophages and monocytes during aging, correlating with an altered tissue environment and the onset of inflammaging. This review aims to provide insights into the connection of inflammatory pathways and altered FAO in macrophages and monocytes from older organisms. We describe a model in which there is an extended activation of receptor for advanced glycation end products, nuclear factor-κB (NF-κB) and the nod-like receptor family pyrin domain containing 3 inflammasome within macrophages and monocytes. This leads to an increased level of glycolysis, and also promotes pro-inflammatory cytokine production and signaling. As a result, FAO-related enzymes such as 5′ AMP-activated protein kinase and peroxisome proliferator-activated receptor-α are reduced, adding to the escalation of inflammation, accumulation of lipids, and heightened cellular stress. We examine the existing body of literature focused on changes in FAO signaling within macrophages and monocytes and their contribution to the process of inflammaging.

The causes and consequences of trained immunity in myeloid cells

“…D). Signaling pathways activated by fatty acids , such as TLR signaling and inflammasome activation, can influence immune responses and trained immunity ( 120 ). Lipid mediators derived from fatty acids, such as prostaglandins, leukotrienes, and resolvins, regulate inflammation and immune cell activation, potentially modulating trained immunity outcomes ( 91 , 120 ).…”

“…Signaling pathways activated by fatty acids , such as TLR signaling and inflammasome activation, can influence immune responses and trained immunity ( 120 ). Lipid mediators derived from fatty acids, such as prostaglandins, leukotrienes, and resolvins, regulate inflammation and immune cell activation, potentially modulating trained immunity outcomes ( 91 , 120 ). Similarly, cholesterol metabolism influences both NLRP3-dependent and independent inflammasome activation and proinflammatory cytokine (e.g., IL-1β) production in innate immune cells ( 121 ).…”

Spotlight on pro-inflammatory chemokines: regulators of cellular communication in cognitive impairment

“…These reduced coenzymes are utilized by the process of oxidative phosphorylation within the mitochondria, releasing their electrons through the electron transport chain (ETC), ultimately converting ADP to ATP ( 72 ). However, when the efficiency of electron transfer in the electron transport chain decreases during oxidation, ROS are generated from incompletely reduced oxygen molecules, especially at complex I and complex III ( 73 , 74 ). The increase in ROS continuously neutralizes the antioxidant enzymes, and the enzyme activity decreases as a result of overwork, leading to a lack of antioxidant capacity and accelerated promotion of oxidative stress.…”