The liver is essential to the body’s energy supply and storage. Mitochondria, the cell’s power plants, are unable to effectively switch between fuel sources in type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD), according to Medical Xpress .
Ketone body metabolism decreases in insulin resistance
Researchers from Heinrich-Heine-University Düsseldorf (HHU), the University Hospital (UKD), and the German Diabetes Centre (DDZ) examined for the first time how well mitochondria in the heart, muscle, liver, and kidney can use the byproducts of fat breakdown – ketone bodies – to make energy. Low-carb diets, exercise, and fasting can all raise ketone body levels.
The study, which was published in eBioMedicine, indicates a possible new target for enhancing energy metabolism in diabetes by demonstrating that energy generation via ketone body metabolism is decreased in insulin resistance, such as in type 2 diabetes and MASLD.
Depending on the availability of nutrients, our body must be able to transition between various energy sources. When glucose is in short supply, the liver produces ketone bodies, which are tiny molecules derived from fatty acids.
They give the kidney, skeletal muscle, heart, and a number of other organs another fuel source. In healthy people, a higher amount of ketones can aid in the creation of energy, but their usefulness in this situation depends on how well the mitochondria can use them.
“Ketone bodies are more than just an alternative fuel in specific conditions-they serve as important fuels for all domains of life to produce energy,” professor Michael Roden said.
Mitochondria generate less energy from ketone bodies
Numerous tissue samples from obese individuals with and without type 2 diabetes or MASLD were analysed by the researchers. The team was able to assess mitochondrial energy generation from ketone bodies directly for the first time using a new method based on a technique called high-resolution respirometry.
The findings were unambiguous: mitochondria generate less energy from ketone bodies in every insulin-resistant state examined. Heart and skeletal muscle cells from overweight people with type 2 diabetes and liver cells from overweight people with MASLD used ketone bodies less effectively for energy production than the corresponding control groups.
“Interestingly, this defect was greater than the overall decline in mitochondrial function, suggesting that ketone body metabolism is particularly vulnerable in insulin resistance,” Dr Elric Zweck said.