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Investigators are examining the impact of the circadian clock on metabolic health


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Dongyin Guan, PhD
Dongyin Guan, PhD

Disruption of circadian rhythms in humans is strongly associated with metabolic disease, including obesity, diabetes, and cardiovascular disease. A panel of experts will discuss how circadian misalignment impacts metabolic health during the Scientific Sessions symposium Zeitgebers (Time-keepers) of Metabolic Health—Resetting the Circadian Clock on Tuesday, June 7. The two-hour session, which begins at 7:30 a.m. CT in La Nouvelle Orleans Ballroom B at the convention center, will also be livestreamed for virtual meeting attendees.

Dongyin Guan, PhD, Baylor College of Medicine, will discuss how environmental factors affect circadian misalignment and metabolic disease, including research from his lab looking at the relationship between metabolic health and the timing of eating and drug administration.

“Our work has been focused on defining the mechanism of circadian control of gene expression in diet-induced obesity mouse models, which could have translational applications for diabetes care regarding optimized timing for medication and meals,” Dr. Guan said.

Among their findings, Dr. Guan and his colleagues have demonstrated that mice, when fed a fattening diet, develop new liver circadian rhythms that simultaneously impact how fat accumulates and burns.

Kristin Eckel-Mahan, PhD
Kristin Eckel-Mahan, PhD

“We further identified the nuclear receptor protein PPAR-alpha as one of the regulators for this obesogenic, diet-induced circadian remodeling,” Dr. Guan said. “Interestingly, giving a short-acting PPAR-alpha drug reduced liver fat more when given in the afternoon than in the morning, suggesting a potential chrono-pharmacological approach for metabolic diseases.”

Dr. Guan believes an optimized schedule for drug administration and eating could be an important preventive approach for shift workers and individuals with sleep disorders, for example, as well as a potential therapeutic strategy for patients with metabolic disorders such as obesity and diabetes.

Kristin Eckel-Mahan, PhD, University of Texas Health Science Center, will discuss research from her lab suggesting that one of the reasons circadian disruption is associated with metabolic disease is because it disrupts the normal 24-hour activity of specific cells within adipose tissue.

“Our data shows that adipocyte progenitor cells undergo diurnal proliferation. In other words, adipocyte precursors divide once a day,” Dr. Eckel-Mahan said. “Under conditions of high-fat diet feeding, this diurnal variation in adipocyte progenitor cell proliferation is lost and cells divide at a constitutively high level, contributing to the hyperplasia and expansion of adipose tissue.”

Additionally, Dr. Eckel-Mahan and her research colleagues found that irregular feeding uncouples adipocyte progenitor proliferation from the 24-hour schedule.

“The main idea supported by our investigation is that adherence to a good diet, as well as a stable 24-hour cycle promotes healthy fat throughout aging,” she said. “Both the timing and quality of dietary intake is important for the normal proliferation of adipocyte progenitor cells during the day/night cycle.”