Study: Genes link circadian clock to eating schedule

A study found that specific genes link a person's circadian clock to their eating schedule.

For most people, the urge to eat a meal or snack comes at a few, predictable times during the waking part of the day. But for those with a rare syndrome, hunger comes at unwanted hours, interrupts sleep and causes overeating.

Now, Salk scientists have discovered a pair of genes that normally keeps eating schedules in sync with daily sleep rhythms, and, when mutated, may play a role in so-called night eating syndrome. In mice with mutations in one of the genes, eating patterns are shifted, leading to unusual mealtimes and weight gain. The results were published in this month's Cell Reports.

"We really never expected that we would be able to decouple the sleep-wake cycle and the eating cycle, especially with a simple mutation," says senior study author Satchidananda Panda, an associate professor in Salk's Regulatory Biology Laboratory. "It opens up a whole lot of future questions about how these cycles are regulated."

More than a decade ago, researchers discovered that individuals with an inherited sleep disorder often carry a particular mutation in a protein called PER2. The mutation is in an area of the protein that can be phosphorylated -- the ability to bond with a phosphate chemical that changes the protein's function. Humans have three PER, or period, genes, all thought to play a role in the daily circadian clock and all containing the same phosphorylation spot.

The Salk scientists joined forces with a Chinese team led by Ying Xu of Nanjing University to test whether mutations in the equivalent area of PER1 would have the same effect as those in PER2 that caused the sleep disorder. So they bred mice to lack the mouse period genes, and added in a human PER1 or PER2 with a mutation in the phosphorylation site. As expected, mice with a mutated PER2 had sleep defects, dozing off earlier than usual. The same wasn't true for PER1 mutations though.

"In the mice without PER1, there was no obvious defect in their sleep-wake cycles," says Panda. "Instead, when we looked at their metabolism, we suddenly saw drastic changes."

Mice with the PER1 phosphorylation defects ate earlier than other mice -- causing them to wake up and snack before their sleep cycle was over -- and ate more food throughout their normal waking period. When the researchers looked at the molecular details of the PER1 protein, they found that the mutated PER1 led to lower protein levels during the sleeping period, higher levels during the waking period, and a faster degradation of protein whenever it was produced by cells.

Panda and his colleagues hypothesize that normally, PER1 and PER2 are kept synchronized since they have identical phosphorylation sites -- they are turned on and off at the same times, keeping sleep and eating cycles aligned. But a mutation in one of the genes could break this link, and cause off-cycle eating or sleeping.

"For a long time, people discounted night eating syndrome as not real," says Panda. "These results in mice suggest that it could actually be a genetic basis for the syndrome." The researchers haven't yet tested, however, whether any humans with night eating syndrome have mutations in PER1.

When Panda and Xu's team restricted access to food, providing it only at the mice's normal meal times, they found that even with a genetic mutation in PER1, mice could maintain a normal weight. Over a 10-week follow-up, these mice -- with a PER1 mutation but timed access to food -- showed no differences to control animals. This tells the researchers that the weight gain caused by PER1 is entirely caused by meal mistiming, not other metabolic defects.

Next, they hope to study exactly how PER1 controls appetite and eating behavior -- whether its molecular actions work through the liver, fat cells, brain or other organs.

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Rare sleep disorder causes woman to eat 2,500 calories while asleep

An interesting article about a sleep disorder causing a woman to eat 2,500 calories in her sleep.

Lesley Cusack, 55, has Nocturnal Sleep-Related Eating Disorder. She said that she only finds out what she’s eaten at night when she looks through the leftovers and trash in the morning.

Csack, who is from Warrington, Cheshire in the UK, binge-eats, chops up food, and tries to cook it while sleeping. She also says she’s tried to eat paint, Vaseline and washing powder. She’s even broken some teeth and bruised herself while trying to cook while sleeping.

"I tend to find opened tins of things or packets and I’ve no idea whether I’ve eaten some of them cold or not,” she said.

‘I’ve found soup in pans, but also in bowls. It all can get rather messy. I’ve put alarms on my doors in the hope it will wake me up. I simply turn it off in my sleep. I’m trying to lose weight but it’s a constant battle. I can follow a diet to the letter but it goes to pot at night,” she added.

"One weekend, I came down to find the cake slice covered in butter. I’d used it while making cheese sandwiches"

"The worst things that I know I’ve eaten are emulsion paint, Vaseline, cough syrup, raw potatoes and soap powder. The night I ate paint was the only time I’ve ever woken up. I can still remember standing in the kitchen touching my mouth and being very confused,” she said.

Due to her night eating, Cusack has gained weight and now weighs about 230 lbs. As a result, she eats fruits and salads during the day and joined a diet club.

Cusack’s doctors have not been able to find an explanation, but Cusack believes she has Nocturnal Sleep-Related Eating Disorder (NSRED).

"I had started to find bits of mess downstairs, but I didn’t realize it was me. It was a while before I worked it out, but when I did, I felt very embarrassed and guilty,” she said.

"There were times when I felt extremely depressed through trying to hide it,” she added.

Cusack, a retired department store manager and divorced mother of three, says she only recently told her family of her disorder. The turning point was the realization that she was going outside to raid the freezer in her shed.

"I was terrified at the thought of leaving the door open or having an accident outside," she said.

"Using the cooker, kettle and sharp knives means it’s only a matter of time before something more serious happens,” she added.

Cusack lives alone.

"My bedding and night clothes are constantly getting stained and need washing. I’m always finding a trail of food leading downstairs,” she said.

‘"The disturbed nights, waking exhausted with stomach cramp, feeling sick and finding food in the bed has become almost normal,” she added.

Dr. Paul Reading, President of the British Sleep Society, said that cases like Cusack’s are rare but not unknown.

"A proportion of adult sleep-walkers will eat and even cook during apparent sleep, often consuming foods they would not normally enjoy," he said.

"Weight gain and guilt are common consequences."

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