Fig. 2

Schematic overview of normal lipid physiology and possible mechanisms involved in lipid disturbances during critical illness. In normal physiology, circulating fatty acid concentration depends on the balance of lipolysis and lipogenesis. Fatty acid uptake is mediated by transporters and passive diffusion and will either enter oxidative pathways to provide ATP or converted to ketone bodies, or stored as triglycerides. The nuclear receptor PPARα is the key transcriptional regulator of these processes. Fatty acids can be converted to immunomodulatory mediators such as ceramides, prostaglandins and specialized pro-resolving mediators. During critical illness, circulating fatty acids and triglycerides are increased and lipid mediators are imbalanced to a pro-inflammatory shift. Elevated lipolysis, impaired oxidative processes and hampered ketogenesis are observed in a context of suppressed PPARα expression. TG: triglyceride; FA; fatty acid; 3HB: beta-hydroxybutyrate; AcAc: acetoacetate; SPMs: specialized pro-resolving mediators; PPARα: peroxisome-proliferator-activated receptor α; ER: endoplasmic reticulum; β-ox: beta-oxidation; TCA cycle: tricarboxylic acid cycle; ATP: adenosine triphosphate; CPT: carnitine palmitoyltransferase; OXPHOS: oxidative phosphorylation; PGs: prostaglandins; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells; STATs: signal transducer of activation (STAT) proteins; AP-1: Activator protein 1; CD36: cluster of differentiation 36. Created with Biorender.com