How Leptin and Ghrelin Regulate Your Hunger and Weight

7 minutes read

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 are leptin and ghrelin [1]. 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.

Leptin and its role in appetite and energy storage

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 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, or how much stored energy a person holds as fat [4]. As leptin levels are proportional to fat mass, the more fat tissue a person has, the more leptin is produced [5]. 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].

Leptin resistance and its effects on metabolism

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].

These are all adaptive responses to help your body conserve energy, as low leptin signals make the body think it’s in starvation mode (lack of appetite suppression means not enough food has been eaten) [10]. 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.

How to fix leptin resistance

“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 energy restriction and weight loss can lead to a lasting reduction in leptin levels and associated decrease in leptin resistance [11].

Is there such a thing as "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, but there's no one specific food that can directly raise your leptin level [12]. 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.

Ghrelin and its role in appetite stimulation

Also known as the “hunger hormone,” ghrelin is the only hormone in your body that induces a feeling of hunger and increases appetite.

Ghrelin production in the body is triggered by three factors:

stomach emptying
stomach stretching
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 and fall after meals [5].

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 its hunger-triggering action (see below).

Levels of ghrelin increase with poor sleep as well as chronic stress and anxiety [13, 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:

Sleep at least 8 hours each night
Exercise regularly
Reduce stress and anxiety (via rest, community interaction, meditation, therapy, etc.)
Use a continuous glucose monitor to track glucose responses to different foods and monitor your diet

How do 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, so it is important to learn more about your body’s response to a meal schedule [15].

The ghrelin-to-leptin ratio is an important determinant of how much people eat. People with a higher ratio tend to eat more, particularly carbohydrates and fats [16]. 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.

How do leptin and ghrelin affect weight loss?

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

One problem is that an overabundance of leptin can lead to insulin resistance. Changes in leptin and ghrelin levels regulate insulin sensitivity: 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:

Eat sufficient, high-quality protein, which has been associated with lower levels of ghrelin [17].
Prioritize sleep, which can help with ghrelin regulation [18]. (Short sleep duration can lead to a rise in ghrelin levels, while chronic sleep deprivation can lead to increases in both ghrelin and leptin.)
Try aerobic exercise to regulate leptin. A clinical trial found that lower resting heart rate (RHR) is linked to lower leptin levels, which suggests that aerobic exercise (to increase cardiovascular strength and decrease RHR) may lower leptin levels [19].
Do strength training to regulate ghrelin. Recent evidence suggests an inverse relationship between fat-free mass and ghrelin, so increasing muscle mass and decreasing fat mass with strength training may help keep ghrelin levels low [20].

References:

Written by: Sarah Jayawardene, MS

Reviewed by: Emily Johnson, MSc RD

Table of Contents

Leptin and its role in appetite and energy storage
Leptin resistance and its effects on metabolism
Is there such a thing as "high-leptin foods"?
Ghrelin and its role in appetite stimulation
How do leptin and ghrelin work together?
How do leptin and ghrelin affect weight loss?
Key takeaways