Scientists studying obesity in mice have found a new type of brain cell that increases appetite, even when the body is full for a long time.
Neuropeptide Y neurons are the focus of many studies on metabolic syndromes. They are particularly abundant in a part of the brain’s hypothalamus called the arcuate nucleus, which produces powerful neurotransmitters that stimulate appetite and delay feelings of satiety.
For many years, it was thought that only one type of neuron expressed neuropeptide Y (NPY), the molecule for which NPY neurons are named, in this part of the brain.
But it turns out that another group of neurons hiding in the hypothalamus also produces appetite stimulants, and not always when it’s advantageous.
Under fluorescent microscopy, an international team of scientists say they have found “a considerable number of NPY-positive neurons”, which have not yet been studied.
Unlike other NPY-producing neurons, this new class also does not co-express the AgRP neurotransmitter, which is why the newly detailed neurons are described as “AgRP-negative”.
In mouse models, these neurons respond rapidly and strongly to fasting conditions, expressing neuropeptide Y and promoting food intake.
On the other hand, when excess energy is stored in the mouse body for prolonged periods, these same neurons continue to express appetite-increasing neuropeptides.
“We found that under conditions of obesity, appetite was primarily driven by NPY produced by this subset of neurons,” says Herbert Herzog, who studies the neurobiology of eating disorders at the Garvan Institute for Medical Research in Australia.
“These cells not only produced NPY, but also sensitized other parts of the brain to produce additional receptors or ‘docking stations’ for the molecule, further increasing appetite.”
It’s a vicious cycle, and one that Herzog and his colleagues are interested in looking into further.
There’s no guarantee that these exact mechanisms of energy intake and expenditure translate to humans (other appetite-promoting neurons can be found as well), but animal models are a useful way to refine neurological research.
Previous studies in mice have shown that when AgRP-positive NPY neurons are restricted in the brain, there are significant reductions in food intake, sometimes to the point of starvation.
But Herzog and his colleagues say these older experiments “missed or missed the contribution” of the other NPY-producing neurons they just found.
In experiments, AgRP-negative neurons were more sensitive to energy dips than AgRP-positive neurons, and responded more strongly to measures to increase appetite.
When the scientists suppressed AgRP-negative NPY neurons in mouse brains, food intake and post-meal weight gain were significantly reduced.
“Our discovery helps us better understand the mechanisms in the brain that interfere with balanced energy metabolism and how they can be addressed to improve health,” says Herzog.
The study was published in Cellular metabolism.
