A new study from the Gladstone Institute of Neurological Disease reported on the discovery of a new mechanism regulating body weight. By removing a receptor known to be present in the brain, mice fed a high-fat diet became protected from obesity, diabetes, and the development of a fatty liver. The study, entitled “p75 Neurotrophin Receptor Regulates Energy Balance in Obesity,” was recently published in the journal Cell Reports.
The p75 neurotrophin receptor (p75 NTR) is most well-known for its role in the brain, where it promotes the growth and survival of neurons. The receptor is, however, present also in other body parts, such as liver and fat cells. Earlier studies found evidence for the involvement of p75 NTR in liver disease and insulin resistance.
The research team investigated the effects of a high-fat diet on p75 NTR, as a high-fat diet is often the root of the problem causing metabolic syndrome.
The study revealed that p75 NTR helps to regulate processes controlling body weight. The team knocked out the gene for the receptor in mice, and after several weeks on a high-fat diet, these genetically modified animals were still lean and healthy — a stark difference from the normal mice on the same diet, which developed obesity, had high insulin levels and signs of fatty liver disease.
The mice without the receptor seemed to use more energy than normal mice since there were no differences in how much the mice ate, or how much they moved.
Bernat Baez-Raja, lead author of the study, commented the findings in a press release: “We’ve identified a novel molecular mechanism that regulates energy expenditure and may help prevent obesity and the metabolic syndrome. 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.”
The team then went on to remove p75 NTR only from fat cells, and observed almost the same positive result. Moreover, when fat cells from the modified mice were transplanted into normal mice, these mice also became protected against the effects of the high-fat diet.
“The robustness of the effect is quite remarkable,” noted senior author Katerina Akassoglou, “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.”
According to the researchers, the next step is to develop small molecules or drugs that can regulate p75 NTR to reproduce this effect. The team believes that the development of agents regulating p75 NTR could lead to new treatments for obesity and metabolic syndrome.