Possible interrelationship between gluconeogenesis and ketogenesis in the liver

Area of Science:

• Biochemistry
• Cellular Metabolism
• Liver Physiology

Background:

• Gluconeogenesis is a vital metabolic pathway for maintaining blood glucose levels.
• Ketogenic substrates are utilized by the liver during fasting or low carbohydrate intake.
• The interplay between gluconeogenesis and ketogenesis is complex and not fully understood.

Purpose of the Study:

• To investigate the effects of various ketogenic substrates on gluconeogenesis from lactate in liver cells.
• To elucidate the role of acetoacetate in modulating gluconeogenesis stimulated by other ketogenic compounds.
• To explore potential mechanisms linking gluconeogenesis and ketogenesis at the mitochondrial level.

Main Methods:

• Incubation of intact liver cells with lactate as a gluconeogenic precursor.
• Addition of various ketogenic substrates including D,L-3-Hydroxybutyrate, acetoacetate, acetate, and oleate at specified concentrations.
• Measurement of gluconeogenesis rates in response to substrate addition.

Main Results:

• D,L-3-Hydroxybutyrate (5 mM) significantly stimulated gluconeogenesis from lactate by 41%.
• Acetate (5 mM) demonstrated a similar stimulatory effect, increasing gluconeogenesis by 49%.
• Acetoacetate did not stimulate gluconeogenesis and, at concentrations up to 40 mM, inhibited the stimulatory effects of acetate, oleate, and 3-hydroxybutyrate.

Conclusions:

• Ketogenic substrates like D,L-3-Hydroxybutyrate and acetate can stimulate hepatic gluconeogenesis from lactate.
• Acetoacetate plays an inhibitory role, potentially by interfering with mitochondrial pyruvate transport.
• A functional interrelationship between gluconeogenesis and ketogenesis, mediated by the mitochondrial pyruvate carrier, is suggested in liver cells.