The brain receptor p75 regulates body weight, according to new research.
The study, conducted by researchers at the Gladstone Institutes, found that lowering levels of p75 neurotrophin receptor (NTR) protected a group of mice from obesity, type 2 diabetes and fatty liver disease.
P75 NTR is more commonly associated with brain cells, but it is present throughout the body, particularly the liver and fat cells. Previous studies have found that p75 NTR is linked to liver disease and insulin resistance.
In this study, the researchers removed p75 NTR from a group of mice, and fed them a diet designed to trigger weight gain. The same diet was fed to a normal group of mice. The normal mice gained weight, had larger fat cells, higher insulin levels and signs of fatty liver disease. On the other hand, the mice without p75 NTR did not gain weight, and they remained healthy after several weeks on the diet.
Both groups of mice ate the same amount and got roughly the same amount of exercise. In this respect, the lack of p75 NTR had little effect. Instead, the researchers noticed that the mice without p75 NTR expended a lot more energy than the normal mice, suggesting that they burned more fat.
Next, the researchers deleted p75 NTR only from fat cells rather than all cell types, in order to find out if it the receptor plays a role in regulating body fat. The effect was the samen, which would suggest that it does. Similarly, when the researchers transplanted fat cells from the altered mice into normal mice, the normal mice experienced the same benefits.
“We’ve identified a novel molecular mechanism that regulates energy expenditure and may help prevent obesity and the metabolic syndromen,” said lead author Bernat Baez-raja, PhD, a research scientist in the Gladstone Institute of Neurological Disease. “The complete protection from obesity and metabolic dysfunction in the study animals, without any differences in appetite of physical activity, suggests that p75 NTR is a key regulator of fat burning.”
Senior author Katerina Akassoglou, PhD, a senior investigator at Gladstone, said: “The robustness of the effect is quite remarkable. 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.”
The researchers hope to develop small drugs capable of regulating p75 that can reproduce the effects observed in the study.
The findings are published in Cell Reports.

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