Hepatic gluconeogenic capability in sepsis is depressed before changes in oxidative capability

Area of Science:

• Biochemistry
• Physiology
• Sepsis Research

Background:

• Plasma alanine levels are elevated in late sepsis.
• Alanine serves as a key gluconeogenic substrate.
• Intra-abdominal sepsis models are used to study metabolic dysfunction.

Purpose of the Study:

• To investigate hepatic gluconeogenic activity in a rat model of late intra-abdominal sepsis.
• To assess the impact of sepsis on glucose production from alanine.
• To evaluate the response to alpha-adrenergic stimulation (phenylephrine) in septic livers.

Main Methods:

• Sepsis induced in rats via cecal ligation and puncture.
• Isolated liver perfusion with Krebs buffer containing alanine.
• Measurement of glucose production and oxygen consumption (VO2).
• Dose-response studies with phenylephrine to assess adrenergic stimulation.

Main Results:

• Glucose production from alanine was significantly depressed in livers from septic rats compared to sham controls.
• Septic livers showed a blunted dose-dependent response to phenylephrine stimulation.
• Oxygen consumption (VO2) was not different between septic and sham livers under tested conditions.

Conclusions:

• Hepatic gluconeogenic capacity is impaired by late sepsis, specifically when using alanine as a substrate.
• The reduced gluconeogenic response to alanine precedes a decline in hepatic oxidative capacity.
• These findings suggest a specific vulnerability in gluconeogenesis during sepsis progression.