My primary research interest is the study of mammalian circadian rhythms. These are 24-h, daily rhythms that are present at every level of biology from gene expression to complex behavior.  The integrity of circadian rhythms is important for good health. For example, shift work, which chronically disrupts circadian rhythms, is associated with increased risk of obesity, cancer, suppression of the immune system and other health problems. In my research I use rodent models to study circadian rhythms and how disrupting these rhythms leads to poor health. Specifically, I am interested in the interplay between the circadian and metabolic systems, with a focus on how circadian disruption contributes to obesity.

The mammalian circadian system is a hierarchial network of oscillators: the master pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus receives information about the light-dark cycle and coordinates the timing of clocks located throughout the brain and body. This organization of circadian clocks results in precise temporal control of behavior and physiology. We found that eating a high-fat diet disrupts this circadian organization and alters daily rhythms of eating behavior and locomotor activity. The overarching goal of my research is to elucidate how the circadian and metabolic systems interact to control physiology and behavior. 

In the lab we measure circadian behavior (eating and activity rhythms) and bioluminescence rhythms in brain and peripheral tissues cultured from transgenic mice. Additionally, we analyze circadian rhythms of whole body metabolism, plasma hormones and lipids, and glucose metabolism. We also translate our basic studies in mice to study circadian rhythms and metabolism in humans. Research in the lab spans multiple disciplines including chronobiology, neuroscience, behavior, physiology, and metabolism.

Clocks & Physiology and Behavior

What are the metabolic consequences of circadian misalignment?

We have shown that consumption of high-fat diet induces misalignment of circadian clocks by advancing the phase of the liver molecular clock (by 5h) while sparing clocks in other central and peripheral tissues. We hypothesize that this circadian misalignment is an early and inciting event in the development of obesity and type 2 diabetes. We are generating new mouse models to measure the direct effects of circadian misalignment of the liver clock on metabolism.  

Estrogen regulation of daily metabolic rhythms

In contrast to males, female mice are resistant to diet-induced obesity. We found high-fat diet does not alter the daily rhythm of eating behavior or the liver clock in females. Thus, we hypothesize that retention of normal daily metabolic rhythms during high-fat diet consumption confers protection from diet-induced obesity in females. We are investigating the molecular and behavioral mechanisms that protect daily rhythms from high-fat diet in females. 

Metabolic benefits of timed exercise

More than 70% of the population experiences a chronic disruption of the their daily, or circadian, rhythms called social jet lag. Social jet lag occurs when your internal circadian clock tells you to sleep late but your alarm clock tells you to wake up early for work or other social obligations. Living against your internal clock, which is what happens during social jet lag, is associated with cardiovascular risk factors and high-risk obesity. In this clinical study, we are testing the hypothesis that exercise at a specific time of day can reduce social jet lag and therefore improve cardiovascular risk factors and insulin resistance. 

Circadian disruption and atherosclerosis

Modern-day lifestyles cause epidemic circadian disruption. Epidemiological studies have linked circadian disruption (e.g. shift work, breakfast-skipping, nighttime eating) to cardiometabolic disease. We are investigating how disruption of circadian rhythms, by exposure to aberrant lighting or eating conditions or, exacerbates atherosclerosis. 

Pendergast Laboratory