VBP Research 2024

Metabolic approach: We targeted metabolic origins of anorexia nervosa(AN) using a mouse model of AN called activity-based anorexia (ABA). We tested the hypothesisthat hunger-evoked hyperactivity, which causesdevastating weight loss and anxiety to AN patients,may be ameliorated by shifting patients’metabolism. We achieved this by replacingstandard diet with high-fat/low-carb ketogenic diet(KG). Results from this study showed that shiftinganimals’ diet to KG significantly reduces weightloss, not due to increased caloric intake butthrough reduction of hunger-evoked excessive exercise.

Psychiatric approach: We targeted the psychiatric origin of AN by testingwhether injections of ABA animals with sub-anesthetic ketamine can ameliorate ABAvulnerability. Our findings are that ketamine doesreduce ABA vulnerability, not only by reducinghunger-evoked hyperactivity but also by increasingcaloric intake. Compared to KG, ketamine’s effect isweaker but longer-lasting. Based on results fromthe metabolic and psychiatric goals, our currentgoal is to examine whether combining KG withketamine reduces ABA vulnerability even more.

Next steps: Results from this study showed that BDNF levels inthe hippocampus are elevated greatly by the ABA-inducing environment, likely due to heightened exercising . However, BDNF level is elevated equallyfor animals fed standard diet or KG. Ketone bodiesare heightened by KG but not by exercise alone orfasting alone or under the ABA-inducing condition ofexercise plus fasting but fed standard diet. In thefuture, we would like to go after the hypothesis thatketone bodies evoke synaptic plasticity to improveresilience against ABA.