According to the Centers for Disease Control (CDC), obesity affected more than 1 in 5 children, adolescents and adults in the U.S. in 2023, contributing to a rise in related health conditions such as Type 2 diabetes, fatty liver disease and cardiovascular issues. For over a decade, intermittent fasting has been a popular weight loss strategy among adults to help address these concerns. But what makes fasting an effective strategy?
Unlike a more traditional three-meals-a-day spread over 12 hours routine, intermittent fasting limits eating to a shorter window each day. Brian DeBosch, MD, PhD, a professor of pediatrics at the IU School of Medicine, stated the positive effects of this diet are thanks to more than simply restricting calorie intake — the liver plays a key role in the process.
“When you fast, your body shifts fuel sources in a way that ensures survival but also carries risks,” DeBosch explained. “Your muscles release nutrients that the liver converts into glucose for energy. However, this creates excess nitrogen, which can be harmful. We discovered that the liver has a built-in mechanism to manage this toxicity while simultaneously enhancing how fuel is augmented during fasting.”
This process is part of the urea cycle, a natural function where the liver removes toxic waste. Activating the urea cycle not only clears excess nitrogen but also boosts fat oxidation, contributing to the positive effects of fasting.
DeBosch also explained that recent studies in humans have shown that when the liver is in a “starvation mode,” such as when carbohydrates are restricted, it continues to signal the body to burn fat.
“When the liver is in starvation sensing mode, it secretes hormones and shifts the entire body's metabolic substrate selection towards fat, and that's a good thing,” he said.
Understanding the liver’s role in fasting and other metabolic processes is a key focus of DeBosch’s research, which he has extensively studied in mice and continues to explore as leader of the nutrition and molecular metabolism research program at the Herman B Wells Center for Pediatric Research.
DeBosch’s research comes at a pivotal time as metabolic health and obesity remain pressing public health challenges. He encourages those striving for a healthier lifestyle to limit excess sugar intake and focus on a balanced diet rich in vegetables, fruits and lean meats. However, as intermittent fasting continues to gain popularity among adults, understanding the science behind its benefits is more important than ever.
“Our future research will dig deeper into ways we can trick the liver into believing that there's no carbohydrate around, to coax it into the starvation state,” DeBosch said. “This could lead to new therapeutic strategies to treat obesity and metabolic diseases.”
When he's not in the lab, DeBosch serves as a pediatric gastroenterologist and co-division chief of gastroenterology, hepatology and nutrition at Riley Children's Health. His clinical work allows him to apply his research directly, sharing insights on liver and gut health with young patients and their care teams.
The ability to both treat patients and drive groundbreaking discoveries is what drew him to a career as a physician scientist. He hopes more aspiring physicians and researchers are drawn to gastroenterology, hepatology and nutrition, so future experts can continue advancing the understanding and treatment of metabolic diseases and related conditions.
“Realizing I could build a career where I treat patients and make discoveries at the same time truly opened my world,” DeBosch said. “I feel fortunate that I can form a perfect marriage between my clinical and scientific practices. I love the immediate gratification of helping someone to feel better in the clinic, as well as the longer-term fulfillment of making a breakthrough that could improve lives long after I’m gone.”
