What is the main source of fuel in sepsis?

Fatty Acids are the Main Source of Fuel in Sepsis

The main source of fuel in sepsis is fatty acids (option b), as there is a significant metabolic shift from glucose to lipid utilization during septic states. 1

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

Evidence Supporting Fatty Acids as Primary Fuel

• Sepsis leads to upregulated lipolysis in adipose tissue, resulting in increased levels of fatty acids and triglycerides in the blood 2
• 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
• Studies have shown that fat appears to be an obligatory fuel in sepsis, while glucose tolerance is often impaired 3

Why Not Other Fuel Sources?

• Glucose (option a): Despite initial hyperglycemia in sepsis, glucose utilization is impaired due to insulin resistance. Glucose is primarily redirected to immune cells for aerobic glycolysis rather than serving as the main systemic fuel 1
• Ketones (option c): While ketone metabolism is altered in sepsis, ketones are not the primary fuel source 2
• Amino acids (option d): Although protein catabolism increases during sepsis, amino acids serve primarily for gluconeogenesis and acute phase protein synthesis rather than as the main energy substrate 4, 2

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
• Carnitine supplementation may be beneficial as it enables the switch from glucose to long-chain fatty acid metabolism during the "sepsis energy crisis" 1
• Dietary interventions with polyunsaturated fatty acids (particularly omega-3 fatty acids) have shown improved survival and decreased bacterial load in experimental sepsis models 5, 6

Common Pitfalls in Managing Metabolic Changes in Sepsis

• 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 beneficial metabolic adaptations, including PPAR-α upregulation, potentially worsening outcomes 1
• Enteral absorption of nutrients may be impaired in sepsis, potentially leading to suboptimal delivery of both nutrients and medications 7