In the past, our research has focused on understanding the pathogenesis and therapies for treatment of severe childhood obesity and Prader-Willi syndrome.

What is Prader Willi Syndrome? 

Prader Willi Syndrome (PWS) is a rare genetic syndrome (affecting 1 in every 10,000–30,000 births) that is typically caused by a loss of function in paternal genes on chromosome 15, leading to hypothalamus dysfunction. It is characterized by overeating (hyperphagia), excess weight gain and developmental delays (physical and mental).

What research have we done? 

Our research in PWS has been used to show that ghrelin (a hunger-inducing hormone) levels are higher in children with PWS. This is different from non-genetic obesity, where ghrelin levels are often lower. This finding suggests that PWS serves as a unique model of ghrelin excess, which may explain the ravenous appetite and progressive weight gain that characterize the condition.  

We also conducted one of the first controlled clinical trials of the use of growth hormone in PWS, providing key data allowing for FDA approval in the United States. Our studies demonstrated that growth hormone reduces adipose tissue, increases lean body mass, increases resting energy expenditure. the data also showed a trend toward improving lung function and sleep quality. 

We have completed metabolic profiling of a cohort of children with PWS compared to healthy children living with obesity. Key findings show that females, but not males, with PWS had hyperghrelinemia, hyperadiponectinemia, hypoinsulinemia, and decreased glycine and tyrosine and BCAA. Collectively, these studies enhance the understanding of the hormonal control of appetite and energy balance and have important, broad implications for understanding general childhood obesity and weight control.

What are some other recent research findings?

In the previous gut microbiota study, our group found a link between the unrelenting feeling of hunger and the altered gut bacteria composition in children with Prader–Willi syndrome (PWS). Gut dysbiosis may be a target for appetite and weight control in PWS. Dietary fibers are well known for their satiating effects and metabolic benefits in humans, which are mediated partly by modulating the gut microbiota. Our group also conducted a three-week fiber intervention study to determine if prebiotic fibers can support the growth of good bacteria and help them thrive in the gut of kids who have PWS. We hypothesized that fiber supplementation would help reduce their excessive appetite and weight gain; this didn't occur in this study, but we did find some other interesting findings. Specifically, we looked at both targeted and untargeted metabolomics analyses to allow us to profile as many metabolites as feasible to maximally cover metabolic processes and pathways. We observed notable shifts in the metabolome and gut microbiota suggesting that fiber supplementation may be helpful, but will need to be individualized for each person based on their current profiles. We are currently conducting similar research in adolescents with obesity and insulin resistance to see if fiber supplementation combined with medications for glucose control can be helpful. Check out the Met-Fiber Study on our Get Involved page for more information!