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Confused circadian rhythm could increase triglycerides

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body clock can change triglyceride levels at cellular levelHaving 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.

Image courtesy of iStockphoto/WebSubstance

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  1. 1. jtdwyer 12:57 am 08/6/2010

    The article states:
    "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."

    This barely hints at a critical factor in my disrupted circadian rhythm: I have to take a max. dosage beta-blocker twice daily, ensuring I sleep at least twice a day. The beta-blocker must be taken twice daily because of its limited duration of effectiveness and its crucial role in controlling a heart condition. The beta-blocker (Carvedilol) mentions increased triglycerides as a side effect, but of course does not explain why.

    My triglycerides had skyrocketed – I now take two other medications to reduce that side-effect to less critical levels, not to mention the Gas-X to reduce their side effects.

    One of the triglyceride lowering meds is Lovaza (prescription omega-3 fatty acid – ‘specially purified’ fish oil). I can attest to its ability to restore clarity of thought, in my case recovering from chemo. I would recommend it to anyone treating high triglycerides for that reason alone, despite its cost – of all the medications I now have to take that’s the only one with a beneficial side-effect!

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  2. 2. DrAkram 6:18 am 08/11/2010

    The increased level of Triglycerides (TGs) accompanying treatment with Carvedilol is a clearly expected side effect ,
    Carvedilol is a beta-blocker and an alpha-blocker at the same time …. when we talk about B2 receptors , we should never forget their role in enhancement of lipolysis , they mediate the process of breakdown of TGs into free fatty acids , thus decreasing the level of TGs in the blood. The only known role of B3 receptors is the enhancement of lipolysis , some medications acting as B3 agonists are mentioned for certain cases of obesity to decrease the body weight by reducing the level of TGs …. so when we block both B2 and B3 receptors , we block the process of lipolysis and as a result lipogenesis increases. great amount of TGs is generated as a result….with sustained treatment of the drug , the level is by far increased than normal values and caused your condition…i hope i managed to give a good explanation and made it someway clear.

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