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The hormone that helps us feel full may also help keep our brain together

There’s more to leptin than meets the eye.

Forgoing an extra helping of spaghetti allows you to feel the smug fullness that comes from a good meal and avoid the awful feeling that you’re about to explode. But you can lose the smugness — this extraordinary show of willpower is possible thanks to a little hormone in your brain called leptin.

Leptin spikes when you are full, and dips when you are hungry. Yet there’s much more to leptin than providing a check on our appetites. Leptin may be involved in the very building blocks of our brain as it develops, as well as several other critical aspects of brain health. Taken together, the evidence hints at important lessons for understanding what intermittent fasting does to the brain. Perhaps more urgently, this knowledge may also help treat depression.

What leptin does in the brain — Leptin works via certain receptors in specific parts of the brain. One of these is the hypothalamus, which is involved in our eating habits. One way to think about these receptors is like a series of bus stops where leptin gets off to go do its job, signaling to the brain and body when it’s had enough to eat. But leptin also plays a role in regulating certain cellular functions in the brain, including the neurotransmitters glutamate and GABA and plays a role in how they transfer information across the brain.

There are also leptin receptors in another part of the brain called the hippocampus, which is involved in emotions and flexible thinking. Brain cells that produce glutamate and GABA there also create new connections — or the synapses between neurons — during early brain development. Leptin may have a hand in this critical process, too, suggesting that its reach goes much further than just signaling satiety.

Leptin may help form connections between brain cells in parts of the newly developing brain.


How leptin affects brain development — In a new study published this week in the journal Science Signaling, researchers provide compelling new evidence for how leptin helps shape the brain as it develops. In the study, the researchers treat hippocampus cells from young mice with leptin and found that it increases the creation of new GABA-related connections between brain cells.

Adding leptin, it seems, enables a still-forming brain to generate more connections — but too much leptin, the authors suggest, is also linked with neurodevelopmental conditions, including autism.

Other preliminary studies show similar effects. If these findings are replicated in future studies, then the evidence indicates that leptin is important to human brain development, too.

This study is not the first time connections have been drawn between leptin levels and cognition, behavior, and other brain-related issues.

Leptin, the brain, and prolonged weight loss — There is a fair amount of research on what happens when leptin levels are too high — for example, in obesity, the increased number of fat cells means that more leptin is produced overall, which can eventually lead to “leptin resistance.” In other words, the brain stops registering the “full” signal after eating enough food.

Too little leptin can also cause problems for the brain.

“You are most likely going to stumble into mental problems, if you have not already at somewhat higher leptin levels, because we don’t really know at what exact leptin level these effects are triggered,” Johannes Hebebrand tells Inverse.

Hebebrand is a professor in the Department of Child and Adolescent Psychiatry at the University of Duisburg-Essen in Germany. He studies the role of leptin in eating disorders. In perhaps the most extreme example of prolonged restrictive eating or fasting, people who have the eating disorder anorexia nervosa also have very low levels of leptin.

The scarcity, or even absence, of leptin, according to one review, may “impair immediate behavioral and stress responses” in people with anorexia. Whether or not a short fast or regular, intermittent fasting could result in similar effects isn’t clear, and would likely vary by person, Hebebrand says. But accounts from intermittent fasting adherents suggest there may be something going on in the brain related to leptin, he says.

Leptin levels are impaired in prolonged periods without food, as in anorexia nervosa.

Getty / Aitor Diago

“Let’s say the person who does this type of one-day fast then experiences an elevated mood, which a subgroup of people do report as a result of 1, 2, 3, 4-day fast,” he says. This elevated mood sensation can have unintended consequences in some groups, he says, and potentially lead to disordered eating, so it is important to talk to your doctor before you engage in any fast or intermittent fasting regimen.

There is evidence from research on people with eating disorders that extreme, prolonged hunger may induce hyperactivity. Mice display this kind of behavior, too — but treating them with leptin, in one study, returned their activities to normal, suggesting leptin may play a regulating role in our behavior, too.

Hebebrand and his team have conducted a number of case studies that suggest treatment with synthetic leptin improves emotion, cognitive skills, and behavior in people with eating problems. In people with anorexia and depression, the treatment tamped down their hyperactivity, and surprisingly, their depression symptoms also improved.

Leptin and depression — Drug treatments for depression can take weeks to kick in, and for some people, such treatments don’t work at all. Based on evidence like Hebebran’s, however, some researchers are becoming increasingly interested in leptin as a potential treatment for depression. The reason why goes back to leptin’s emerging role in brain development and forming brain connections.

Leptin appears to be critical in encouraging “neuroplasticity” — essentially, how well the brain responds to and learns from change and new stimuli, forming new pathways and connections. A disruption in neuroplasticity in the brain can contribute to depression, according to one oft-cited scientific review.

According to a separate review on leptin’s role in depression, activating leptin receptors in the brain can also activate a chemical pathway that’s related to the effects of some fast-acting antidepressants, like ketamine, for example. Essentially, this pathway is involved in the “maturing” of synapses, and the formation of new connections between neurons. Because scientists still aren’t exactly sure how antidepressants work, it is too early to say with surety exactly what leptin is doing in the brain to combat depression symptoms. But several animal studies hint at promising results — leptin does lead to some improvement, and it appears to have a similar effect to Prozac in mice. In one study, a rat model of chronic stress had lower levels of leptin, suggesting in turn that boosting the hormone may help treat the stress.

Human studies are murkier when it comes to leptin’s possible link to depression. Humans with major depression have been found to have higher-than-average leptin levels — but in some individuals, leptin levels are much lower than expected. More research is needed to tease out leptin and depression in people.

Leptin may yet turn out to be the unsung hero of the brain — and, of course, help us to be well-fed without overdoing it.

The National Eating Disorders Association helpline can be accessed here.

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