From studies on mice, researchers in the US have discovered that disrupting the body clock or circadian rhythm could interfere with a normal 24 hour cycle of high and low triglycerides in a way that leaves them at a high level all the time, potentially raising the risk of atherosclerosis and heart disease.

You can read how Dr M. Mahmood Hussain, a professor in the Department of Cell Biology and Pediatrics, at the State University of New York Downstate Medical Center in Brooklyn, and colleagues, arrived at these findings in a paper published online in the journal Cell Metabolism on 4 August.

High levels of blood fat or lipids (eg triglycerides and cholesterol) are a risk factor for atherosclerosis, where plaque builds up inside artery walls, eventually making them narrower and increasing the risk of heart attacks and strokes. In the US there is a national goal to reduce levels of lipids in the blood.

In this study, Hussain and colleagues from SUNY Downstate Medical Center and the University of Utah School of Medicine in Salt Lake City, studied two groups of mice: one group of normal lab mice and the other genetically bred to have a “broken” body clock.

As nocturnal animals, the normal lab mice had a sleep wake cycle where they were active at night, when they did most of their eating, and sleeping during the day.

The researchers also observed that over the course of 24 hours, the blood levels of triglycerides in the normal mice fluctuated: doubling or peaking when they were asleep and reaching their lowest point at night when the animals were most active.

The mice that were genetically bred to have a broken sleep-wake cycle (the researchers referred to them as “clock mutants”) had no regular pattern of wake and sleep: they ate both during the day and during the night and were overall less active.

For the clock mutant group, the researchers observed that their triglyceride levels varied hardly at all over a 24 hour period: they stayed relatively high all the time.

When they further investigated the link between the body clock and triglyceride levels they found that a protein called CLOCK, a core component of the circadian circuitry, controls another protein called MTP (microsomal triglyceride transfer protein) that carries triglycerides in the bloodstream. So when CLOCK is disrupted, so is MTP.

Hussain and colleagues concluded that their findings indicate that disruptions in circadian regulation might cause high levels of blood lipids (hyperlipidemia).

They noted that major metabolic disorders like metabolic syndrome and obesity are characterized by high levels of blood lipids, and if these findings are replicated in humans, then perhaps the effect of drugs that target MTP as a way to lower triglyceride levels may vary depending on when they are taken each day.

Hussain explained in a statement that perhaps we can now start thinking about drug timing in controlling disease states:

“The dose needed may vary depending on the time of day,” said Hussain.

The study also supports the idea that perhaps activities that disrupt the body clock, such as staying up till the early hours and travelling between different time zones, also affect lipid metabolism, he added.

“Diurnal Regulation of MTP and Plasma Triglyceride by CLOCK Is Mediated by SHP.”
Xiaoyue Pan, Yuxia Zhang, Li Wang, M. Mahmood Hussain.
Cell Metabolism, Volume 12, Issue 2, 174-186, 4 August 2010
DOI: 10.1016/j.cmet.2010.05.014

Additional source: Cell Press.

Written by: Catharine Paddock, PhD