Appetite and eating may seem pretty straightforward—we eat when we are hungry—but the story of how our appetite is regulated is a complicated one, involving many different signaling molecules distributed in networks that involve various parts of the brain.

Understanding the underlying biology of appetite is central in the effort to discover more effective ways of treating eating disorders such as anorexia nervosa and bulimia, as well as obesity.

A team of investigators from the University of Arizona led by 2016 and 2010 BBRF Young Investigator Haijiang Cai, Ph.D., has now identified a group of neurons in an oval-shaped area within a brain region called the BNST (bed nucleus of stria terminalis). The neurons in this oval area, which are distinguished from other nearby cells because they express a protein called PKC-delta, form a circuit.

The researchers performed experiments demonstrating that in the presence of different signals, this circuit can act to inhibit or stimulate eating. This suggests that neurons in the circuit or the signals that activate and inhibit them could potentially be a target of future interventions to manage eating disorders.

 

The team was trying to understand neural mechanisms underlying a type of anorexia that afflicts people who have certain chronic illnesses including cancer and HIV infection. Anorexia involves weight loss and an inability to maintain a normal weight. Sometimes it is triggered by an irrational fear of gaining weight. In the type of anorexia studied by the Arizona researchers, the illness is triggered, rather, by immune system signals which interfere with normal signaling that governs appetite.

Clues from past research led the team to focus on the BNST, which is one of several brain areas known to be involved in the regulation of feeding. In particular, they knew of experiments in which activation of neural inputs into the BNST as well as activation of outputs from the BNST had the effect of increasing food intake in laboratory mice. No prior study, however, had observed the impact of directly stimulating neurons within the BNST.

When the researchers directly activated neurons expressing PKC-delta in an oval section of the BNST, they noticed that feeding behavior decreased. “Silencing” these same neurons had the opposite effect, leading the animals to eat more. These results indicated to the team that “besides inflammation-associated anorexia, these [BNST] neurons mediate bi-directional control of general feeding,” they reported in the journal Nature Communications.

Noting that the neurons forming the BNST circuit also receive inputs from other brain areas known to be involved in feeding behavior, the researchers suggest that the newly discovered circuit “might function as a central hub in integrating” various circuits that regulate feeding. How the different components work together—and how problems in the circuitry might cause eating disorders—is a subject for future research, say the researchers. So far, they are able to say that the specific neurons and circuit they have just identified in the BNST could serve as possible “therapeutic targets for inflammation-associated anorexia, [and] also other feeding-related illnesses including eating disorders and obesity.”