Specific brain circuit controls compulsive overeating and sugar addiction

New research discovered a specific brain circuit that controls compulsive overeating and sugar addiction.

Compulsive overeating and sugar addiction are major threats to human health, but potential treatments face the risk of impairing normal feeding behaviors that are crucial for survival. A study published January 29th in the journal Cell reveals a reward-related neural circuit that specifically controls compulsive sugar consumption in mice without preventing feeding necessary for survival, providing a novel target for the safe and effective treatment of compulsive overeating in humans.

"Although obesity and Type 2 diabetes are major problems in our society, many treatments do not tackle the primary cause: unhealthy eating habits," says senior study author Kay Tye of the Massachusetts Institute of Technology. "Our findings are exciting because they raise the possibility that we could develop a treatment that selectively curbs compulsive overeating without altering healthy eating behavior."

Compulsive overeating is a type of reward-seeking behavior, similar to drug addiction. But the major difference between the two behaviors is that eating is required for survival, underscoring the need to tease apart brain circuits involved in compulsive overeating versus normal feeding to develop safe and effective therapies. Tye and her team suspected that a neural pathway from the lateral hypothalamus to the ventral tegmental area might play an important role in compulsive overeating because these brain regions have been implicated in reward-related behaviors such as eating, sexual activity, and drug addiction.

To test this idea, Tye and her team used a technique called optogenetics, which involves genetically modifying specific populations of neurons to express light-sensitive proteins that control neural excitability, and then delivering either blue or yellow light through an optic fiber to activate or inhibit those cells, respectively. Activation of the pathway from the lateral hypothalamus to the ventral tegmental area caused well-fed mice to spend more time feeding and increased the number of times mice poked their nose into a port to receive a sugar reward, even when they had to cross a platform that delivered foot shocks to get to the reward. By contrast, inhibition of the same pathway reduced this compulsive sugar-seeking behavior without decreasing food consumption in hungry mice, suggesting that different neural circuits control feeding in hungry animals.

In an independent study also published January 29th in Cell, Garret Stuber of the University of North Carolina School of Medicine and his team similarly used an optogenetic approach in mice to identify neurons in the lateral hypothalamus that control both feeding and reward-seeking behavior. By imaging the activity of hundreds of individual lateral hypothalamus neurons as the mice freely explored an area with food or worked to obtain a sweet reward, they further uncovered distinct subsets of neurons that either mediate food-seeking behavior or respond to reward consumption.

According to Tye, it makes sense that brain circuits evolved to support binging on scarce, sugary foods whenever these valuable sources of energy become transiently available during certain seasons. But in the winter, it might be adaptive for separate neural circuits to drive hungry animals to eat whatever type of food is available but to consume less overall to ration out limited resources.

"However, in our modern day society, there is no scarcity of palatable foods, and high-sugar or high-fat foods are often even more available than fresh produce or proteins," Tye says. "We have not yet adapted to a world where there is an overabundance of sugar, so these circuits that drive us to stuff ourselves with sweets are now serving to create a new health problem. The discovery of a specific neural circuit underlying compulsive sugar consumption could pave the way for the development of targeted drug therapies to effectively treat this widespread problem."

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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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Study: People who sleep less eat more

A new study in children show that those who sleep less are more likely to be overeaters.

Young children who sleep less eat more, which can lead to obesity and related health problems later in life, reports a new study by UCL researchers.

The study found that 16 month-old children who slept for less than 10 hours each day consumed on average 105kcal more per day than children who slept for more than 13 hours. This is an increase of around 10% from 982kcal to 1087kcal.

Associations between eating, weight and sleep have been reported previously in older children and adults, but the study, published in the International Journal of Obesity, is the first to directly link sleep to energy intake in children under the age of 3 years. The association was observed before differences in weight emerged, strongly suggesting that energy intake is a key pathway through which sleep contributes to weight gain in early childhood. While the exact causes remain unclear, the regulation of appetite hormones may become disrupted by shorter sleeping patterns.

The study, funded by Cancer Research UK, involved 1303 UK families in the Gemini birth cohort, monitoring sleep when children were 16 months old and diet at 21 months old.

"We know that shorter sleep in early life increases the risk of obesity, so we wanted to understand whether shorter sleeping children consume more calories" explains Dr Abi Fisher of the Health Behaviour Research Centre at UCL. "Previous studies in adults and older children have shown that sleep loss causes people to eat more, but in early life parents make most of the decisions about when and how much their children eat, so young children cannot be assumed to show the same patterns.

"The key message here is that shorter sleeping children may prone to consume too many calories," says Dr Fisher. "Although more research is needed to understand why this might be, it is something parents should be made aware of."

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