Body’s own fat metabolism fights against harmful effects of sugar, study finds

19 Sep 2017 --- Researchers from Aarhus University in Denmark have discovered a metabolite that reveals how the body's fat metabolism provides protection against the harmful effects of sugar. The researchers have indicated this has the potential to explain the chemical link between a low-carbohydrate diet and healthy aging.

The study, which made the front cover of the journal Cell Chemical Biology, helps to uncover new aspects of the metabolic process in living organisms, according to the Aarhus University press release.

"Previous research partly based on animal experiments using mice and monkeys shows that a diet with less sugar and more fat protects against diseases such as diabetes, Alzheimer's and cancer,” says Mogens Johannsen, who is professor of chemical biology at the Department of Forensic Medicine at Aarhus University and one of the leading capacities in the research partnership.

“At the same time, it has also been known that methylglyoxal causes age-related diseases. We have found a new metabolite that demonstrates an alternative chemical detoxification of methylglyoxal when we burn fat,” Johannsen adds.

“It is a surprising discovery, as ketones in themselves can lead to the harmful sugar metabolite methylglyoxal,” continues Johannsen. “The explanation may be a delicate balance between creation and detoxification. In any case, this illustrates that biological systems are enormously complex.”

Piece of the puzzle
For several years, medical researchers, doctors and dieticians have known that a low-carbohydrate diet and plentiful fat can prevent a range of lifestyle and age-related diseases and thus promote healthy aging, the Aarhus University press release notes. But until the discovery of the metabolite, researchers from around the world had not been able to explain why this is the case. They had just been reasonably certain that the energy metabolism and its chemical intermediates (metabolites) played a central role.

The interdisciplinary team of researchers from Aarhus University has now found what the press release calls “more than just an important piece of the puzzle – a piece that suggests that the puzzle that is our metabolism looks somewhat different than science has so far believed.”

On a general level, the researchers have discovered that the fat-metabolism in the cells takes place simultaneously with a detoxification of the harmful substances from the blood sugar, which can avert the damage that can, in turn, lead to age-related diseases such as diabetes, Alzheimer's and cancer. This indicates that humans have a detoxification system that the researchers were not previously aware of, according to the press release.

Unexpected chemistry
The detoxification takes place in an unexpected chemical process – unexpected because it happens without the involvement of the enzymes that science has so far focused on in understanding the metabolism and the decomposition of sugar.

The newly-discovered process involves one type of metabolite, the ketone acetoacetate, which originates from the body’s fat metabolism, capturing and inhibiting another type of metabolite, methylglyoxal, which originates from the body's sugar metabolism.

The process is important because methylglyoxal is a reactive metabolite, meaning that it is toxic for the cells. It plays a major role in age-related diseases like the aforementioned diabetes, Alzheimer's and cancer. This means that untreated diabetics have increased concentrations of sugars and methylglyoxal in their blood. They also have increased amounts of ketone substances.

In chemical terms, what happens in the process between the two metabolites is that a third metabolite – 3-HHD, which does not have the harmful effects of methylglyoxal – emerges. The Danish research team is the first to find 3-HHD in blood from people who lacked insulin and/or had fasted the night before – a condition known to give ketosis.

From lab to humans
Johannsen does not doubt the value of research into the role of ketones and reactive metabolites in biological aging.

“Now we have evidence for saying that ketones can minimize the amount of harmful methylglyoxal in living organisms, and that is a discovery that gets noticed, as it involves two of the most debated substances within biological aging and late diabetic complications. Moreover, these substances react with each other,” Johannsen explains.

The study is relevant for developing treatments of people suffering from complications after diabetes, in particular patients with late diabetic complications such as neuropathy, which can be very painful, the press release adds.

“One perspective could be to follow a diet with fewer carbohydrates and more fat. The fat helps to encapsulate and destroy the sugars that cause the pain,” says Johannsen. However, he also emphasizes that clinical trials will be needed to establish this aspect before he would recommend particular diets.

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