What is the main source of fuel in sepsis?

Main Source of Fuel in Sepsis

The main source of fuel in sepsis is fatty acids. 1

Metabolic Alterations in Sepsis

• 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
• This 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

Glucose Metabolism in Sepsis

• 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
• In later stages of sepsis, hypoglycemia develops due to peripheral glucose usage and anorexia, further limiting glucose as a viable fuel source 1

Role of PPAR-α in Fatty Acid Metabolism

• 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 1
• Studies show that PPAR-α knockout mice display reduced FAO and decreased survival in sepsis models 1

Ketone Bodies in Sepsis

• Despite increased fatty acid mobilization, ketone production is actually suppressed in sepsis 1
• This occurs because inflammation down-regulates the enzymes involved in ketone production 1
• Recent clinical trials suggest that ketogenic diets may improve outcomes in critically ill sepsis patients, indicating that ketones are not the primary fuel source but could be beneficial if supplemented 1

Amino Acid Metabolism

• While amino acid metabolism is altered in sepsis, amino acids do not serve as the primary fuel source 2
• A study examining fuel sources in critically ill patients found that the type of parenteral nutrition (glucose vs. glucose-fat combination) did not significantly influence whole body protein dynamics, suggesting amino acids are not the dominant energy substrate 3

Clinical Implications

• 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
• Dietary interventions with omega-3 fatty acids have shown improved survival and decreased bacterial loads in experimental sepsis models, highlighting the importance of fatty acid quality 4, 5
• Carnitine supplementation may be beneficial as it enables the switch from glucose to long-chain fatty acid metabolism during the "sepsis energy crisis" 1

Common Pitfalls and Caveats

• 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 1

In conclusion, while all macronutrients show altered metabolism during sepsis, fatty acids represent the main source of fuel, with lipolysis being significantly upregulated to meet the increased energy demands of the host response to infection.