A New Way to Treat Anorexia?

Anorexia nervosa, commonly referred to as simply ‘anorexia’ is a serious disease - in the US, more than one person dies every hour. In today's society, around 10% of people with an eating disorder suffer from anorexia. Typically, people suffering with anorexia are in early adolescence and young adulthood. It’s a particularly difficult condition to treat because of the interplay between psychological and physiological factors, manifesting as the body essentially attempting to starve itself. In anorexia, the brain, due to complex underlying causes, urges food restriction even when the body is malnourished. Despite the seriousness of anorexia, the scary truth is that there is no simple way to treat it. There are no US Food and Drug Administration-approved drugs; instead typical treatment paths involve simultaneously addressing both psychological and physical problems. However, recent research by Hui Chen et al., has highlighted a potential new experimental treatment that may offer a new avenue for drug development.

How a ‘hunger protein’ may offer potential for treating anorexia

Acyl CoA binding protein (ACBP), is an appetite-stimulating protein conserved across all four eukaryotic kingdoms, namely Animalia, Plantae, Fungi, and Protista, and in some eubacterial species. ACBP consists of four domains, each of which are shaped like a bowl and have a highly-exposed Acyl-CoA-binding site. In mice, anorexia caused by chronic resistant stress (CRS) was associated with a decrease in the level of ACBP secretion. 

In this latest research by Hui Chen et al., a chemical-genetic system was designed which could express more ACBP protein in mice. In transgenic mice, higher levels of ACBP were associated with a reduction in weight loss and a bigger appetite. In addition, the group discovered that daily intravenous injections of ACBP protein or subcutaneous implantation of pumps releasing ACBP mimicked the effect of the chemical-genetic system, offering alternative solutions.

You may be wondering: “how does this help people who are struggling with anorexia”? The team took plasma samples of anorexia patients and found that those with lower levels of ACBP had a poorer prognosis compared to those who have a higher level of ACBP. So, as in mice, it seems our ACBP production level plays a key part in how our body regulates appetite level. Importantly, this discovery showcases the potential of ACBP as a target for drug development. Despite this correlation, the path to therapeutic development will not be straightforward because in humans the root cause of anorexia has a large mental health component, and while this treatment might help treat the disorder on a physical level, it does not target the typically complex underlying mental health issues at play within anorexia patients.

Is there a possibility that ACBP-protein regulation could do the opposite effect and help treat obesity? 

Recent research by Bravo-San Pedro et al., explored the opposite to the Hui Chen research group, whereby they neutralised the effect of ACBP by way of systemic injection of neutralising monoclonal antibodies in mice. The results showed that injections gave an anorectic effect (reduced appetite). While GLP-1 receptor agonist drugs like the increasingly popular Wegovy (semaglutide) are showing immense promise in treating obesity, continuing to explore different treatment avenues will be vital. 

Final thoughts

Taken together, both these studies affirm the important role ACBP plays in appetite regulation and affirms the protein as an interesting target for medical research to further explore its use in treating eating disorders and chronic diseases like obesity.