Ketone ester administration improves glycemia in obese mice

Area of Science:

• Metabolic Physiology
• Endocrinology
• Nutritional Science

Background:

• Ketones, such as β-hydroxybutyrate (βOHB), serve as alternative ATP substrates during fasting.
• Skeletal muscle ketone oxidation is linked to obesity-related hyperglycemia.
• Inhibiting succinyl CoA:3-ketoacid CoA transferase (SCOT) can improve hyperglycemia.

Purpose of the Study:

• To test if increased circulating ketone levels worsen glucose homeostasis via muscle ketone oxidation.
• To investigate the effect of exogenous ketone ester administration on glucose tolerance in lean and obese mice.
• To examine the impact of ketones on insulin secretion from isolated islets.

Main Methods:

• High-fat diet-induced obesity model in C57BL/6J mice.
• Oral administration of ketone ester (KE) or placebo followed by glucose tolerance tests.
• Isolated islet perifusion experiments to measure insulin secretion.

Main Results:

• Exogenous KE administration increased circulating βOHB levels.
• Glucose tolerance improved in obese mice treated with KE, independent of muscle SCOT activity.
• The R-isomer of βOHB significantly increased insulin secretion in isolated islets from obese mice.

Conclusions:

• Acute elevations in circulating ketones promote glucose-lowering effects in obesity.
• The glucose-lowering effect is not mediated by increased skeletal muscle ketone oxidation.
• Further research is needed to clarify the role of β-cell ketone oxidation in insulin secretion.