Timing is everything for liver disease sufferers, study suggests

Timing is everything for liver disease sufferers, study suggests

Eating at the right time could be a crucial factor in avoiding disease, a team led by Weizmann Instiute scientists discovers

Illustrative photo of overweight people hiking at the Wingate institute in Israel. (Moshe Shai/Flash90)
Illustrative photo of overweight people hiking at the Wingate institute in Israel. (Moshe Shai/Flash90)

You are what you eat is the dictum most dieters follow in order to shed excess pounds, but new research by the Weizmann Institute suggests that when you eat is as important, if not more so. A study recently published in the journal Cell Metabolism shows that merely changing meal times in mice affects the level of triglycerides in the liver. The study could eventually prove to be very important to human sufferers of high liver triglycerides, which can lead to all manner of maladies, including chronic liver disease.

Scientists know that many biological processes follow a set timetable, with levels of activity rising and dipping at certain times of the day. These 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 the environment. Disruption to this timing system has been shown to be detrimental to health, both in animal and human studies. For example, numerous studies have shown that night shift workers, who are on the job when the body naturally expects to be sleeping, have higher levels of obesity, heart disease, and diabetes, among others.

The study, conducted by Weizmann postdoctoral fellow Yaarit Adamovich and the team in the lab of Dr. Gad Asher of the Weizmann Institute’s Biological Chemistry Department, together with scientists from Dr. Xianlin Han’s lab in the Sanford-Burnham Medical Research Institute, Orlando, Florida, sought to study the role of circadian rhythm in the accumulation of fats (lipids) in the liver. The study was conducted on lab mice, quantifying hundreds of different lipids present in the mouse liver. The scientists discovered that a certain group of lipids, namely the triglycerides (TAG), exhibited circadian behavior. TAG levels rose throughout the morning, peaking about eight hours after sunrise, before falling again at night.

That was as expected, but that the pattern held true even in mice in which the “body clock gene” had been removed — meaning that, technically, they were no longer bound by the body’s circadian rhythms — was unforeseen. Yet the accumulation of lipids in the liver followed a circadian pattern in these mice as well — although the rhythm was somewhat different, with levels cresting at 12 hours into the mice’s day, instead of the 8 hours the other mice exhibited.

“These results came as a complete surprise: One would expect that if the inherent clock mechanism is ‘dead,’ TAG 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 TAG — the eating habits of these mice might play a role,” she said.

Usually, mice consume 20% of their food during the day and 80% at night. However, in mice lacking a functional body clock, the team noted that they ingest food constantly throughout the day. As food consumption was spread throughout the mice’s waking hours, eating in and of itself was seen as not directly impacting the liver’s lipid levels.

But in a variation of the experiment, scientists found evidence that nighttime eating was connected to fatty liver in mice. After they provided the same amount of food — but restricted 100% of the feeding to nighttime hours — the team observed a dramatic 50% decrease in overall liver TAG levels. Their conclusion: There is a clear connection between meal times and liver fat, with the time at which TAG accumulation occurs, as well as its levels, determined by body clocks together with timing of meals.

Why this is so is the next area the teams will explore, but some lessons can be learned even now, said Dr. 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, he added.

“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,” Asher said. What this means for humans remains to be seen, but for those with fatty liver and other diseases, consuming the lion’s share of their calories in the daytime, as humans are diurnal creatures, might be worth trying.

read more: