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Metabolic Health

Leptin and Ghrelin: How These Hormones Regulate Your Hunger

Written by: Sarah Jayawardene

Reviewed by: Emily J., MSc RD

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cooked dishes in gray ceramic bowls
2022-09-26

7 minutes

The sensation of hunger is a basic biological impulse — you eat to live. But how does your body sense hunger and fullness? How does it know when to start and stop eating?


Hunger is controlled by interactions between your brain and hormones in your body. These signaling molecules are often featured in articles on dieting and weight loss, but they also have roles in overall metabolic health. 

Two of the major hormones that regulate hunger and control food intake[1] are leptin and ghrelin. Ghrelin is a hormone secreted in anticipation of food and is associated with hunger. Leptin is a hormonal indicator of satiety or fullness.

Simply put, leptin tells you to stop eating, whereas ghrelin tells you to eat.

What We Know About Leptin

When you eat, both the fat cells within fat tissue (called adipocytes) and the cells lining the small intestine (called enterocytes) create leptin. Leptin interacts with neurons in the hypothalamus of the brain to produce appetite-suppressing signaling molecules[2]. When you become full, these molecules tell you to stop eating. Leptin is often referred to as the “satiety hormone” because it leads to the feeling of satiation, appetite suppression, and increases in energy expenditure[3]. 

Leptin also helps regulate energy storage – it allows your brain decide when to store excess energy as body fat. This makes leptin an indicator of long-term energy status[4], or how much stored energy a person holds as fat. As leptin levels are proportional to fat mass[5], the more fat tissue a person has, the more leptin is produced. Because of that, leptin levels are generally lower in people who are lean.

Leptin also directly influences insulin – and vice versa – in that leptin inhibits insulin action, while insulin release increases leptin production[6]. In other words, having more insulin circulating in the body increases leptin — so if you’re insulin resistant and have high circulating insulin, you may also have high leptin. Both hormones play an important role in regulating food intake and energy metabolism, and both are crucial to maintaining normal blood glucose levels. 

Leptin is also important for increasing insulin sensitivity, especially in people who are overweight or obese. It’s been called the “obesity hormone” because a lack of leptin (or a resistance to it, as we will see) results in increased feeling of hunger, which can lead to excessive weight gain[7]. 

How to Fix Leptin Resistance 

When you overeat, your body's leptin receptors become less sensitive. Similar to how continued drinking of alcohol leads to dulled senses, continued eating (causing too much leptin made) leads to dulled leptin receptors. It has been observed that people with higher fat mass have decreased sensitivity to leptin[8]. Their bodies will continue to secrete more and more leptin to compensate — however, over time the brain may no longer recognize leptin because their bodies aren't responding properly to it. 

When the normal leptin signaling process breaks down like this, it is called leptin resistance[9]. 

Leptin resistance results in increased appetite, more food consumption than normal, and slowed metabolism. These are all adaptive responses to help your body conserve energy, as low leptin signals make the body think it’s in starvation mode[10] (lack of appetite suppression means not enough food has been eaten). However, in the case of overeating – where your body is getting enough food, but leptin resistance makes your body think you need to eat more – this combination of effects leads to weight gain and decreased metabolic health.

“Fixing” leptin resistance is complicated and highly variable from person to person. Some short-term studies suggest that caloric restriction or fasting can lower leptin levels and restore leptin sensitivity, while longer-term research indicates both restriction of energy and weight loss can lead to lasting reduction in leptin levels and associated decrease in leptin resistance[11].

The Myth of High-Leptin Foods 

It's commonly believed that certain foods — mainly food high in protein — can raise leptin levels, and lead to decreased hunger (and decreased weight). Studies have found that eating protein can create a feeling of fullness[12], but there's no one specific food that can directly raise your leptin level. There are many different factors, known and still needing to be researched, involved with leptin regulation.
The bottom line is more research is needed to fully understand how high fat and protein foods can affect leptin levels, but they are still a great option to increase satiety and promote stable blood sugar.

What We Know About Ghrelin

Also known as the “hunger hormone,” ghrelin is the only hormone in your body that induces a feeling of hunger and increases appetite. Ghrelin acts in opposition to leptin, by stimulating appetite when energy stores are low. As a result of ghrelin's effects, eating cues continue until body weight and fat reserves are replenished.

Ghrelin production in the body is triggered by three factors: stomach emptying, stomach stretching, and low blood sugar levels (why a spike and “crash” in blood sugar might make you feel hungry). It is mainly produced by endocrine cells of the stomach, and production stops when the stomach is distended due to food intake. As a result of its effects on appetite, ghrelin plays an important role in feeding behavior. Ghrelin levels rise before meals in anticipation of food[5] and fall after meals.

How to Suppress Ghrelin

Although ghrelin is indirectly decreased by high leptin levels, there are no known direct suppressors of ghrelin. Instead of getting rid of ghrelin entirely, research suggests specific methods to keep ghrelin levels “lower” and limit it’s hunger-triggering action (see below).

Levels of ghrelin increase with poor sleep[13] as well as chronic stress and anxiety[14]. In contrast, levels of ghrelin stay stable with continued exercise and a nutritious diet. To keep ghrelin levels in check, it’s important to follow healthy habits such as:

How Leptin and Ghrelin Work Together 

Throughout the day, leptin levels rise and fall in response to energy needs — as energy stores increase or decrease, so do leptin levels. Ghrelin has an inverse relationship with leptin: when leptin is high, ghrelin is low; when leptin is low, ghrelin is high. It is well established that there is a diurnal rhythm (the day/night cycle that human metabolic and biological processes typically align with) in leptin and ghrelin levels[15], so it is important to learn more about your body’s individual response to a meal schedule

The ghrelin-to-leptin ratio has been shown to be an important determinant of how much people eat. People with a higher ratio tend to eat more[16], particularly carbohydrates and fats. The cyclical relationship between the two hormones is key to understanding how they work together, since the breakdown of the relationship is part of what causes metabolic health problems, like weight gain and insulin resistance.

The Relationship Between Leptin, Ghrelin, and Weight Loss

When you’re overweight (or after initial weight loss), leptin levels remain elevated and ghrelin levels remain low[1], making it difficult to continue to lose weight. 

One problem is that an overabundance of leptin can lead to insulin resistance. Insulin sensitivity is regulated by changes in leptin and ghrelin levels: leptin inhibits insulin production, while ghrelin directly stimulates insulin release. Research suggests that there may be a link between leptin resistance and insulin resistance (the body's inability to process sugar properly), as well as with other hormonal and metabolic issues. In addition to leptin resistance, insulin resistance could be the main reason you aren't losing weight.

Key Takeaways

Although the primary function of leptin and ghrelin is to regulate hunger, they also play a key role in efficient metabolism. Ghrelin increases the feeling of hunger and desire for food intake. In contrast, leptin increases satiety, which decreases hunger and desire for food. A person's weight is controlled by complex interactions among these two hormones, as well as insulin.

Here are ways to start regulating your leptin and ghrelin levels through diet, exercise, and sleep:

References

  1. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X.2006.00270.x
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354688/
  3. https://nutritionj.biomedcentral.com/articles/10.1186/s12937-018-0427-x 
  4. https://www.nature.com/articles/nm1010-1097
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2202913/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602983/
  7. https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC4069066&blobtype=pdf
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354688/
  9. https://pubmed.ncbi.nlm.nih.gov/23359004/
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354688/
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651558/
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564867/   
  13. https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0010062
  14. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1467-789X.2010.00776.x
  15. https://pubmed.ncbi.nlm.nih.gov/33703941/
  16. https://nutritionj.biomedcentral.com/articles/10.1186/s12937-018-0427-x
  17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179508
  18. https://pubmed.ncbi.nlm.nih.gov/32537891/
  19. https://pubmed.ncbi.nlm.nih.gov/14678289/
  20. https://pubmed.ncbi.nlm.nih.gov/36088864/

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