A study of “dented” internal clocks seems to have provided evidence for a theory as to why people who work late or irregular hours are susceptible to weight gain and diabetes. High rates of shift workers gain weight and develop diabetes, which has been attributed to a mismatch between their internal clocks and their schedules, so researchers from the Perelman School of Medicine created a related mismatch by altering the function of a molecule within the brains of mice that shortened their circadian rhythms from 24 to 21 hours. These mice gained more weight, had higher blood sugar, and fattier livers, all of which were corrected by changing their environment to a 21-hour “day.”
“When the external world doesn’t match the internal body’s cycles, metabolism pays the price,” says the study’s senior author, Mitchell A. Lazar, the director of Penn Medicine’s Institute for Diabetes, Obesity, and Metabolism, and the Ware Professor of Diabetes and Metabolic Diseases. “We saw this in our study, and we believe that this happens similarly when people work odd hours that don’t align with how human bodies are wired.”
Published in Science Advances, the researchers led by Lazar and primary investigator Marine Adlanmerini, a postdoctoral researcher in Lazar’s lab, sought to explore circadian desynchrony, a theory in which a disruption or alteration to a person’s innate, internal clock leads to poor outcomes. Shift workers—those who may work long hours, overnight, or with irregular rest periods in between work—are subject to this, which could be why they appear to be at higher risk for obesity, diabetes, and metabolic diseases including having a liver that retains more fat.
“One potential explanation is that the internal clock of the mice missing REV-ERB was running at odds with the 24-hour day, which led to metabolic stress on the body,” Lazar says.
A way that was “fixed” was when the researchers adjusted the length of the mice’s “day” in the lab to match their malfunctioning internal clock: 21-hour days with 10.5-hour cycles of light and dark to match their 21-hour internal clock. When this happened, the mice with the altered clocks no longer were as susceptible to the ill-effects of the unhealthy diet.
That correction seemed to fall in line with the circadian desynchrony theory: Once the internal clock and the day lined up again, metabolism appeared to operate at its normal, healthy rate.
This story is by Frank Otto. Read more at Penn Medicine News.
