We all have an internal clock. It's why we get sleepy at night and sometimes wake up without an alarm. But that's not the only biological clock ticking in our bodies. Every tissue and organ has a circadian rhythm, according to Kevin Koronowski, PhD, assistant professor in the Department of Biochemistry and Structural Biology in the Long School of Medicine and researcher with the Barshop Institute.
"Sleep is the most obvious circadian rhythm that we all know, but our internal clock will coordinate essentially all of our bodily functions throughout day and night," Koronowski said. "Not just the sleep-wake cycle, but our immune response, our metabolism, our cardiovascular function, like blood pressure, heart rate, body temperature. Our cognition will change throughout the day."
Koronowski's UT Health San Antonio lab studies circadian rhythm, and right now he's trying to understand the rhythm of fat metabolism. This process is divided into dayparts, with a period for eating and a period for fasting. When you're awake and eating, your body stores fat. When you're asleep and fasting, it burns it.
"This is all fine and normal when we eat a healthy, balanced diet. This is what we would call homeostasis," Koronowski explained. "But what we think is that this clock mechanism of the transition from fasting to feeding might actually be detrimental when we have a high-fat diet, or we have a metabolic disease condition."
This rhythm is regulated, in part, by two proteins. Peroxisome proliferator-activated receptors (PPARs) facilitate fat burning, and cryptochrome (CRY) puts the brakes on PPARs so fat burning stops. But what if there's still fat left to burn? "We think this inhibition on PPAR alpha might prevent us from burning excess fat when we need to do that. This clock mechanism that tries to stop fat burning every day might actually be maladaptive or detrimental," Koronowski said. His theory: if you could disable that daily brake, people with metabolic disorders might be able to burn fat around the clock, not just part of the day.
The American Heart Association is funding this research because circadian misalignment and metabolic dysfunction are direct drivers of cardiovascular disease. "So we're trying to understand exactly how this works and then test how it influences the outcomes in the metabolic disease situation," Koronowski said. When they have this information, Koronowski said they can begin to develop therapeutic strategies to disrupt or "somehow sidestep" the circadian rhythms that sometimes inhibit fat metabolism.
Science & Medicine is a collaboration between TPR and The University of Texas Health Science Center at San Antonio, about how scientific discovery in San Antonio advances the way medicine is practiced everywhere.
