Ginger clue in diabetes treatment

Eating ginger may turn out to be a useful self-administered treatment for diabetes and obesity, new research indicates.

Such a conclusion is still extremely tentative – so don’t rush off to the greengrocer’s just yet – but the possibility arises from experiments that seem set to usher in a paradigm shift in managing how our bodies store and convert fat.

A team led by US tissue biologist Shingo Kajimura of the University of California, San Francisco, has uncovered a previously unknown molecular pathway by which mammals are able to repurpose a pair of proteins to burn fat and turn it into heat – protecting the body against cold.

The discovery solves a persistent mystery regarding the conversion of so-called “beige fat”, a transitional type of deposit that can turn energy-storing white fat into the heat-producing brown type.

Beige fat was discovered in 2015, also by Kajimura’s team.

Mouse-based studies found that animals with good reserves of beige fat were protected from diabetes and obesity – because they were better able to burn off excess calories and consequently reduce white fat reserves.

The mystery, however, was how this was achieved. Research more than two decades ago identified a protein – known as “uncoupling protein 1” (UCP1) – that exists only in brown and beige fat cells. UCP1 works to direct energy flow into cell mitochondria, causing it to give off heat rather than bio-available energy. It does this when external cold demands that the body warm itself and other mechanisms – primarily shivering – either aren’t sufficient or aren’t available.

On the basis of UP1’s role, it was reasonable to test the proposition that if the protein was removed, the fat-burning transition would not happen, resulting in the retention of white fat and the consequent elevation of diabetes and obesity risk. Studies in mice, however, found that this was not the case.

It was also discovered that some mammals – pigs, for instance – do not produce UCP1 but are still able to burn fat to keep warm.

The conclusion was stark: beige fat’s transitional properties were entirely independent of the protein.

"This was conceptually very surprising to us and for the field, because UCP1 has been the only known thermogenic protein for over 20 years," Kajimura recalls.

Now, however, the mystery has been solved. With lead author Kenji Ikeda and colleagues, Kajimura has uncovered a previously unknown role for two other proteins, called SERCA2b and ryanodine receptor 2 (RyR2).

The pair are well known, but it was previously thought that their functions were limited to regulating the input and use of calcium within cells.

The new research, however, found that when confronted by cold, the proteins operate in concert – the scientists compare the reaction to revving a car engine while applying the brake – to produce a lot of heat and burn a lot of fuel simultaneously. The fuel burned, of course, is glucose.

“Now that we've found that beige fat burns glucose using SERCA2b, it explains many things,” Kajimura says.

“This is why mice become diabetic when we reduce beige fat, but disrupting UCP1 does not cause diabetes, and this is why mice are protected from diabetes in the presence of more beige fat.”

The fat-burning reaction caused by the two proteins was big enough and consumed enough fuel to affect whole-body glucose levels. This suggests that regulating their activity holds potential therapeutic outcomes for the management of diabetes and obesity. It may also help patients subject to sudden internal temperature drops better control their symptoms.

The scientists note that the research potentially explains a food-related phenomenon often observed but poorly understood. Many people testify that eating ginger warms up the body – and now it seems that the idea is not without potential evidence.

It has been noted that a ginger extract known as gingerol activates proteins in the same family as SERCA2b, opening up the possibility that it may have a role to play in influencing the body’s ability to convert white fat into the beige and brown varieties.

The research is published in the journal Nature Medicine.

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