August 3, 2010 | 2
Having a mixed up body clock has been linked to a vast array of ailments, including obesity and bipolar disorder. And researchers are still trying to understand just how these cyclical signals influence aspects of our cellular and organ system activity.
Now, a study published online August 3 in Cell Metabolism shows that in mice, a disrupted circadian rhythm spurs an increase in triglycerides—heightened levels of which have been linked to heart disease and metabolic syndrome in humans.
To find this link, researchers compared normal lab mice to those bred to have dysfunctional sleep-wake cycles. As nocturnal animals, the control mice had the lowest levels of triglycerides at night, when they were most active, and higher levels during the daytime rest period. The mice with out-of-whack cycles kept confused hours, fed longer and were less active overall. These mutant mice also had far less fluctuation in their triglyceride levels.
"We show that the normal up and down [of triglycerides] is lost in clock mutants," M. Mahmood Hussain, of the Department of Cell Biology and Pediatrics at the State University of New York Downstate Medical Center in Brooklyn and coauthor of the paper, said in a prepared statement. The mutant mice had "high triglycerides all the time," he noted.
Hussain and colleagues found that the CLOCK protein, which is implicated in establishing the body’s circadian rhythm, also plays a role in moderating microsomal triglyceride transfer protein (MTP), which is in charge of moving triglycerides through the blood. Thus, when CLOCK was not functioning properly, neither was the triglyceride transporter MTP.
A disrupted body clock has already been linked to weight gain, but "this study establishes a molecular link between circadian physiology and plasma lipid metabolism," the researchers noted in their paper.
By pinpointing these more precise links, researchers hope to be able to eventually develop therapeutics for humans. And because the body’s daily cycle seems to be so crucial in controlling lipid levels, the findings also might help inform important treatment details such as dosing and pill-popping instructions. With these and other recent circadian-linked findings, "we can start to think about [the role of] drug timing in controlling disease states," Hussain said.
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