Scientists studying obesity in mice have found a new type of brain cell that boosts appetite, even when the body is satiated 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, producing potent neurotransmitters that stimulate appetite and delay feelings of fullness.
For many years, only one type of neuron was thought to express neuropeptide Y (NPY), the molecule that gives NPY neurons their name, in this part of the brain.
But as it turns out, another group of neurons hiding in the hypothalamus also produces appetite boosters – and not always when it's advantageous.
Under fluorescent microscopy, an international team of scientists says they have found "a considerable number of NPY-positive neurons", which have yet to be studied.
Unlike other NPY-producing neurons, this new class does not also co-express the neurotransmitter AgRP, which is why the newly detailed neurons are described as 'AgRP-negative'.
In mouse models, these neurons respond quickly and strongly to fasting conditions, expressing neuropeptide Y and promoting food intake.
On the flip side, when excess energy is stored in the mouse body for extended periods, these same neurons keep expressing neuropeptides that boost appetite.
"We found that under obese conditions, appetite was mostly driven by NPY produced by this subset of neurons," says Herbert Herzog, who studies the neurobiology of eating disorders at the Garvan Institute of Medical Research in Australia.
"These cells did not only produce NPY but also sensitized other parts of the brain to produce additional receptors or 'docking stations' for the molecule – supercharging appetite even further."
It's a vicious cycle, and it's one that Herzog and his colleagues are interested in studying further.
There's no guarantee that these exact mechanisms of energy intake and expenditure will translate to humans – there also may be other appetite-promoting neurons to be found – but animal models are a useful way to hone further neurological research.
Previous studies on 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 colleagues say these older experiments "missed or overlooked the contribution" of the other NPY-producing neurons they just found.
In experiments, AgRP-negative neurons were more sensitive to drops in energy than AgRP-positive neurons, and they responded more strongly with appetite-boosting measures.
When 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 a balanced energy metabolism and how they may be targeted to improve health," says Herzog.
The study was published in Cell Metabolism.