This Protein May Keep You Lean on Any Diet

It’s no replacement for hard work and good nutrition but this protein might eliminate the negative health effects of bad diets.

Recently, Gladstone Institute researchers have discovered an unlikely mechanism involved in the storage and utilization of body fat, called P75 neurotrophin. This protein might even reduce or eliminate the negative health effects caused by obesity-inducing diets, and provide improved energy.

In the initial round of research, the P75 neurotrophin receptors were experimentally removed in a group of mice. These receptors are what allow the neurotrophin proteins to do their job, and without the receptors, the proteins were rendered useless. Then these mice and normal mice were fed a high fat diet to see what would happen.

The diet the mice ate was enough to make the normal mice obese, with large fat cells, higher insulin levels and insulin sensitivity, and the beginnings of fatter liver disease. So the diet wasn’t great for their health to say the least. But the mice with their P75 neurotrophin receptors removed had no such effects. Remarkably, they remained healthy, without liver or insulin problems, and they resisted weight gain, even remaining lean.

Except that they obviously burned more fat, it isn’t entirely clear why the p75 depleted mice resisted weight gain. The mice all ate the same diet, and had the same amount of physical activity. And yet they still had greater energy expenditure, perhaps through some mechanism like Non-Exercise Activity Thermogenesis (NEAT). In humans, NEAT is the major factor in adaptive thermogenesis that changes with alterations in diet. Essentially, you fidget less, and make fewer energy burning choices outside of exercise which eventually add up. For the mice without P75 neurotrophin receptors, it added up to enough of an effect to remain lean on a diet substantial enough to cause fatty liver disease.

Now this was a study done on mice, so we don’t know what effect a P75 neurotrophin intervention would have on people. Theoretically, without experimentally eliminating this receptor, humans could take a drug which blocks the receptor to find out if the effects are consistent.

A possibly alarming effect in human beings could be that, in the human brain, P75 neurotrophin is involved in neuron growth and neuron survival. Whatever effects it has in mice, this seems to be a pretty important receptor in human beings. Although some drug or genetic therapy might reduce the negative effects of high calorie diets in humans, we’d have to know at what cost.

As if anticipating the possible harm to human beings, the researchers conducted a follow up experiment in which the receptor was removed only from fat cells in the body of the mice, but not in the brain. “Since neurotrophins and their receptors control the communication between the brain and peripheral organs, they could be new therapeutic targets with implications in both metabolic and neurologic diseases,” said the senior investigator, Katerina Akassoglou. So it is possible to essentially remove this signal while leaving the P75 neurotrophin receptors in the brain intact. This could theoretically reduce some of the potential side-effects.

Indeed, the experiment to remove the P75 neurotrophin receptors in just the fat cells was as successful in eliminating metabolic disease and body fat as the initial experiment.

The researchers suggest that the development of a drug to perform this task would be the next step. Presumably, the tests would be performed in animal experiments long before something was developed for human use. Should it prove successful, we could have a human drug that eliminates some lifestyle diseases. Of course, there would be further uses for the drug, like helping athletes stay lean while on high calorie diets that promote longer-duration exercise.

As incredible as the possible benefits to athletes and non-athletes could be, we are still a very long way off from knowing if this could be safe or effective in humans. Until then, good old-fashioned hard work and healthy eating will do the trick.


1. Gladstone Institutes. “Brain receptor regulates fat burning in cells: Decreasing levels of p75 neurotrophin receptor prevented obesity and metabolic diseases in mice fed a high-fat diet.” ScienceDaily. ScienceDaily, 12 January 2016.