Fatty Acids as the Primary Fuel Source in Sepsis

Metabolic Changes in Sepsis

In sepsis, there is a dramatic shift in fuel metabolism, with lipolysis becoming the predominant catabolic process upregulated during infection 1
This metabolic shift is mediated by inflammatory cytokines, adrenalin, glucocorticoids, and glucagon, which upregulate hormone-sensitive lipase, leading to increased breakdown of fat stores 1
Plasma triglycerides and free fatty acids (FFAs) can increase up to four-fold in septic patients, indicating their mobilization as the primary fuel source 1
While hyperglycemia is commonly observed in sepsis, glucose utilization is actually impaired due to significant insulin resistance 1

The metabolic shift to fatty acid utilization is facilitated by Peroxisome proliferator-activated receptor-alpha (PPAR-α), a key transcription factor that induces fatty acid oxidation (FAO) pathways 1
PPAR-α signaling and the resulting fatty acid oxidation are essential for survival during sepsis 1

Amino acids serve primarily for gluconeogenesis and acute phase protein synthesis rather than as the main energy substrate, according to the Society of Critical Care Medicine 2

The metabolic shift to fatty acid utilization in sepsis can lead to toxic accumulation of FFAs in organs if not properly utilized, causing organ damage and mitochondrial dysfunction 1
Carnitine supplementation may be beneficial as it enables the switch from glucose to long-chain fatty acid metabolism during the "sepsis energy crisis" 1
Excessive administration of glucose during sepsis can worsen outcomes by promoting excessive immune activation through enhanced glycolysis, as recommended by the American College of Critical Care Medicine 1
Despite fatty acids being the primary fuel source, the accumulation of FFAs without proper utilization can be detrimental, causing organ damage 1
Force-feeding during sepsis may interfere with beneficial metabolic adaptations, including PPAR-α upregulation, potentially worsening outcomes 1