Slashing levels of p75 neurotrophin receptor (NTR) in fat cells could offer a new avenue of research for obesity research, according to a new preclinical mouse study from the Gladstone Institutes.
P75 NTR, which is involved in neuron growth, also appears to regulate metabolic activity linked to weight gain. A group of mice engineered with reduced levels of p75 NTR were able to stay lean, while normal mice fed the same diet rapidly gained weight and experienced a spike in insulin levels with evidence of fatty liver disease. The results were published in Cell Reports.
"The complete protection from obesity and metabolic dysfunction in the study animals, without any differences in appetite or physical activity, suggests that p75 NTR is a key regulator of fat burning," says lead author Bernat Baez-Raja, a research scientist in the Gladstone Institute of Neurological Disease.
In a related mouse study, they also determined that reducing p75 NTR in fat cells had the same effect as replicating the cuts in all cells. Now they want to develop small molecules that can reduce p75 NTR and see how it might work in humans.
"The robustness of the effect is quite remarkable," says senior author Katerina Akassoglou, a senior investigator at Gladstone. "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."