The mechanics behind the liver’s response to feeding and fasting are explained in a paper published earlier this week in Cell Metabolism. Minutes after you eat a meal, as nutrients rush into your bloodstream, your body makes massive shifts in how it breaks down and stores fats and sugars. Within half an hour, your liver has made a complete switch, going from burning fat for energy to storing as much glucose as possible.
Salk researchers say the liver can have such a speedy response to food because liver cells store up pre-RNA molecules involved in glucose and fat metabolism. This finding could facilitate the development of new therapies against obesity and diabetes.
"The switch from fasting to feeding is a very quick switch and our physiology has to adapt to it in the right time frame," says Satchidananda Panda, a professor in the Salk Institute's Regulatory Biology Laboratory and lead author of the paper. "Now we know how our body quickly handles that extra rush of sugar."
It was known that a RNA-binding protein called NONO was implicated in regulating circadian rhythms in the body. But Panda’s team wondered whether NONO had a specific role in the liver. They analyzed levels of NONO in response to feeding and fasting in mice. After the animals ate, speckled clumps of NONO suddenly appeared in their liver cells, newly attached to RNA molecules. Within half an hour, the levels of corresponding proteins—those encoded by the NONO-bound RNA—increased.
"After mice eat, it looks as if NONO brings all these RNAs together and processes them so they can be used to make proteins," adds Panda.
When mice lacked NONO, it took more than three hours for levels of the same proteins, involved in processing glucose, to increase. During that time lag, blood glucose levels shot up to unhealthy levels. Since blood glucose levels are also heightened in diabetes, the researchers think that the mice without NONO may act as a model to study some forms of the disease.
Image: Salk researchers discover how liver responds so quickly to food. Image shows NONO protein immunostained green in liver cells after a meal. Blue indicates cell nuclei. Image courtesy of Salk Institute.