Home » Health » Is that why diets don’t work? Leaving hungry mice without food and opting for sex because of leptin

Is that why diets don’t work? Leaving hungry mice without food and opting for sex because of leptin

Surely hungry mice would always choose food over sex if they had the choice? Not if you give them a shot of leptin.

German researchers have studied the effect of certain hormones and neurotransmitters in the mouse brain that regulate appetite. They watched live through a tiny microscope into the brains of ‘free-behaving’ animals in the lab.

The life of a lab mouse is simple and manageable. He roams around in the limited space he has, eating and drinking, and if he gets the chance to mate, he does. But what if you gave a hungry mouse the choice between sex and food? German researchers looked at the neurological effect of the appetite-suppressing hormone leptin. The conclusion is that the attention of fairly hungry (but not extremely hungry) mice shifts from eating and drinking to mating when their brains are stimulated with leptin.

But one thing at a time
“Behaviorally, we can only do one thing at a time, so our brain must somehow calculate what is the most rewarding behavior, or what our most pressing need is,” says lead researcher Tatiana Korotkova of the University of Cologne. Her team excited neurons in the lateral hypothalamus, one of the main ‘feeding centers’ in the brain. The focus was on neurons with leptin receptors and neurons that produce the neurotransmitter neurotensin (also involved in hunger and thirst stimuli). They discovered to their surprise that these neurons were also involved in controlling social behavior and in balancing the need for social contact with the need for food and drink.

“We were surprised to find that the lateral hypothalamus links eating and drinking to social behavior,” says German researcher Anne Petzold. “Activating leptin receptor neurons causes mice to prioritize social interaction even though they are acutely hungry or thirsty. This is a useful biological mechanism because a sex partner is not available at all times of the day. The mice ignore their hunger or thirst in order to mate.”

Useful biological mechanism
The team used tiny microscopes to image and record the activity of individual brain neurons as the mice explored an enclosed space. “It was ideal that we could capture the functioning of neurons in an animal that could behave freely,” explains Korotkova. “We were able to see beautifully how neuronal activity changes during certain behaviors, and we could very precisely monitor and manipulate the activity of individual cells.”

Interest in opposite sex
There was a group of ‘acutely hungry’ mice, whose food suddenly ran out overnight, and a group of ‘chronically hungry’ mice, who had had little or nothing to eat for five days. According to the researchers, the situation in which the acutely and chronically hungry mice found themselves also occurs regularly in the wild, because food is not always available. The team looked at how the mice’s priorities changed according to their hunger levels and compared the two groups with a control group of mice that were able to eat their fill every day. They found that leptin receptor neurons were less active during eating and became more active when interacting with mice of the opposite sex, but not when interacting with same-sex mice. The researchers then stimulated specific neurons with light patterns and chemicals to see if and how this changed the behavior of the mice.

Is that why diets don’t work?
Stimulation with leptin had little effect on the behavior of the fed mice – which were generally more interested in socializing than in eating – but when the researchers activated the leptin receptor neurons of acutely hungry mice, they saw something surprising: they suddenly moved a lot slower towards the food, ate less, and spent more time with potential mates. However, the chronically hungry mice remained focused on eating even after leptin stimulation. The appetite remained unchanged and they did not see their counterparts of the opposite sex even after a shot of leptin. “We’re apparently dealing with a neurological system that can only regulate mild to moderate hunger, but doesn’t work if you’re hungry like a bear, says Korotkova. “This brain circuitry may be one reason why diets don’t work: it’s fine to reduce your food intake for a short time, but it doesn’t work if you want to keep the low calorie intake for a long time.”

Less social
After activating neurotensin neurons, the mice became less social and more thirsty. They drank a lot more and no longer saw both their potential partners and mice of the same sex. “We often assume that a brain cell has one specific function, but we have discovered that one neuron can process multiple stimuli and thus coordinate different behaviour. That is much more efficient than different cell types somehow communicating with each other to perform the same task,” explains Korotkova. “We want to build on this new knowledge and gain a better understanding of how the functioning of these brain cells changes in patients suffering from eating disorders or (morbid) obesity.”

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