Just changing meal times could have a significant effect on the levels of triglycerides in the liver – at least in mice. The results of this Weizmann Institute of Science study, published recently in Cell Metabolism, have important implications not only for the potential treatment of metabolic diseases, but also may have broader implications for most research areas in the life sciences.

Many biological processes follow a set timetable, with levels of activity rising and falling at certain times of the day.

Such fluctuations, known as circadian rhythms, are driven by internal “body clocks” based on an approximately 24-hour period – synchronized to light-dark cycles and other cues in an organism’s environment. Disruption of this optimum timing system in both animal models and in humans can cause imbalances, leading to such diseases as obesity, metabolic syndrome and fatty liver disease. Night-shift workers, for example, are at higher risk of such disorders.

Postdoctoral fellow Dr. Yaarit Adamovich and the lab team of Dr. Gad Asher of the Rehovot institute’s biological chemistry department studied the role of circadian rhythm in the accumulation of lipids in the liver. Together with scientists from Dr. Xianlin Han’s lab in the Sanford-Burnham Medical Research Institute in Orlando, Florida, they quantified hundreds of different lipids in mouse livers.

Among their findings was that a certain group of lipids called triglycerides exhibited circadian behavior – with levels peaking about eight hours after sunrise. The scientists were amazed to find that daily fluctuations in this group of lipids persist even in mice that lacked a functional biological clock, albeit with levels reaching their peak at a completely different time – 12 hours later than the natural schedule.

“These results came as a complete surprise: One would expect that if the inherent clock mechanism is ‘dead,’ triglycerides could not accumulate in a time-dependent fashion,” said Adamovich. So what was making the fluctuating lipid levels “tick” if not the clocks? “One thing that came to mind was that, since food is a major source of lipids – particularly triglycerides – the eating habits of these mice might play a role.”

Usually, mice consume a fifth of their food during the day and the rest at night, but mice that lack a functional clock eat constantly throughout the day. This observation excluded the possibility that food is responsible for the fluctuating patterns seen in triglyceride levels in these mice. When the team proceeded to check the effect of an imposed feeding regimen upon wild type mice, however, they were in for another surprise: After they provided the same amount of food – but restricted all of the feeding to nighttime hours – the team observed a dramatic 50 percent decrease in overall liver triglyceride levels. These results suggest that the time at which lipid accumulation occurs, as well as its levels, are determined by the clocks together with timing of meals.

The details of the mechanism that drives the actual fluctuating behavior are yet to be discovered.

Asher: “The striking outcome of restricted nighttime feeding – lowering liver triglyceride levels in the very short time period of 10 days in the mice – is of clinical importance.

Hyperlipidemia and hypertriglyceridemia are common diseases characterized by abnormally elevated levels of lipids in blood and liver cells, which lead to fatty liver and other metabolic diseases. Yet no currently available drugs have been shown to change lipid accumulation as efficiently and drastically as simply adjusting meal time – not to mention the possible side effects that may be associated with such drugs.

” Of course, mice are nocturnal animals, so to apply these results to humans, the timetable would need to be reversed. Time is a crucial element in all biological systems, so these findings are likely to impact biological research in general. Circadian clock mechanisms function even in cultured cells, so research results could vary depending on the time at which samples are analyzed, or, with animals, their feeding regimen might significantly affect the experimental outcomes. In other words, when it comes to designing experiments, scientists should be aware that “timing is everything.”

HIGH MARKS FOR SOURASKY

Tel Aviv Sourasky Medical Center has been accredited for it excellence by JCI (Joint Commission International) for its high quality of medical care. Of 1,300 qualitative criteria for the seal of approval, the municipal/state medical center earned positive marks on 1,280 of them – making it among the best hospitals in the world. The US-based commission awarded Sourasky with its citation last month. The criteria included doctor and nurse performance, cleanliness, patient safety, staff training, protecting the rights of patients and their families, prevention of infections and giving medication safely, among others.

JCI was chosen by the Health Ministry to carry out hospital examination and accreditation in Israel. Five commission experts came to assess the hospital; the head of the team said: “I do three hospital accreditation assessments a month around the world, but your results are rare, and you can be proud of them. Sourasky director-general Prof. Gabi Barbash congratulated his employees for the achievement of meeting strict international standards.

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