Fuel Metabolism in Sepsis

Metabolic Alterations

In sepsis, there is a significant shift from glucose to lipid utilization as the primary energy source, with lipolysis of lipid stores being the main catabolic process upregulated during infection 1
The metabolic shift is mediated by inflammatory cytokines, adrenalin, glucocorticoids, and glucagon, which upregulate hormone-sensitive lipase 1
Plasma triglycerides and free fatty acids (FFAs) can increase up to four-fold in septic patients, indicating their mobilization as a primary fuel source 1

While hyperglycemia is commonly observed initially in sepsis, glucose utilization is actually impaired due to significant insulin resistance 1
Glucose is redirected to immune cells to promote aerobic glycolysis and immune function, rather than serving as the primary systemic fuel 1

Peroxisome proliferator-activated receptor-alpha (PPAR-α) is a key transcription factor that facilitates the metabolic shift from glucose to lipid utilization during sepsis 1
PPAR-α signaling induces fatty acid oxidation (FAO) pathways, which are essential for survival during sepsis 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" 3

Excessive administration of glucose during sepsis can worsen outcomes by promoting excessive immune activation through enhanced glycolysis 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 the beneficial metabolic adaptations, including PPAR-α upregulation, potentially worsening outcomes 2