Timing is everything
New findings stemming from Dr. Gad Asher’s laboratory at the Weizmann Institute of Science suggest that merely changing meal times could have a significant effect on the levels of triglycerides in the liver. The results of this study may lead to new treatments for metabolic diseases.
Many biological processes follow a set timetable, with levels of activity rising and dipping at certain times of the day. Such fluctuations, known as circadian rhythms, are driven by internal “body clocks” based on an approximate 24-hour period – synchronized to light-dark cycles and other cues in an organism’s environment. Disruption to this optimum timing system in both animal models and in humans can cause imbalances, leading to diseases such as obesity, metabolic syndrome, and fatty liver. Night-shift workers, for example, have been shown to have higher incidence of these diseases.
Dr. Gad Asher and his team in the Department of Biological Chemistry, together with scientists from Dr. Xianlin Han’s lab in the Sanford-Burnham Medical Research Institute, Orlando, U.S., have been studying the role of circadian rhythms in the accumulation of lipids in the liver of mice. Their findings, recently published in Cell Metabolism, have important implications for the potential treatment of metabolic diseases, and are expected to impact most research areas in the life sciences.
Separately, in a recent event at the Zappa Live Music Club in Tel Aviv, one of the PhD students in Dr. Asher’s lab, Ziv Zwighaft, presented his work on this subject. The event was held by WeizmannVibe, the “next generation” group of the Israeli Friends of the Weizmann Institute of Science. WeizmannVibe provides a social and professional network to executives and entrepreneurs at various stages of their careers, and keeps them abreast of news and research at the Weizmann Institute.
In this study, the scientists quantified hundreds of different lipids present in the mouse liver. They discovered that a certain group of lipids, namely the triglycerides (TAG), exhibit circadian behavior, with levels peaking about eight hours after sunrise. The scientists were astonished to find, however, that daily fluctuations in this group of lipids persist even in mice lacking a functional biological clock, albeit with levels cresting at a completely different time – 12 hours later than the natural schedule.
One plausible explanation was that, since food is a major source of lipids – particularly TAG – the eating habits of these mice might play a role. Usually, mice consume 20 percent of their food during the day and 80 percent at night. However, in mice lacking a functional clock, the team noted that they ingest food constantly throughout the day. This observation excluded the possibility that food is responsible for the fluctuating patterns seen in TAG levels in these mice.
Another surprising finding was that after they were provided the same amount of food, but only during nighttime hours, there was a dramatic 50 percent decrease in overall liver TAG levels. These results suggest that the time at which TAG 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 TAG 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 in order to construe these results for humans, the timetable would need to be reversed.