LEPTIN – Friend or Foe of Fat Burning

Dear blog readers and loyal Peak customers,

Contrary to what was once believed, our adipose tissue is not dead tissue. Visceral abdominal fat, in particular, is highly metabolically active. Body fat is therefore also referred to as the body’s largest endocrine organ.

Hunger and satiety do not occur randomly in the body but are regulated, among other things, by certain hormones. One of the most important is leptin.

Today, I’d like to explain in more detail what leptin is all about, how it behaves in certain contexts—such as in relation to body fat percentage and calorie intake—and how you can manipulate it to your advantage when your goal is fat burning.

What is leptin, and where is it found?

Leptin is a cytokine-like, protein-based hormone consisting of 167 amino acids. The name “leptin” is derived from the Greek word for “thin,” “lepros.”

It is produced mainly by fat cells (adipocytes) and in very small amounts in the placenta, gastric mucosa, bone marrow, breast epithelium, skeletal muscle, pituitary gland, and hypothalamus (brain).

How Does Leptin Work?

Leptin is an appetite-suppressing substance and plays an important role in regulating fat metabolism as well as in the long-term regulation of hunger and satiety.

Serum leptin levels serve as an indicator of the body’s energy status; that is, leptin provides the hunger and satiety centers with information about available fat stores—in other words, the body’s energy reserves.

A leptin deficiency leads to a decrease in energy expenditure through certain mechanisms in the body. This results in a decrease in thyroid-related markers such as TSH and levothyroxine (T4), gonadotropins (the sex hormone-stimulating LH and FSH), and testosterone.

Leptin is hormonally regulated; it inhibits insulin and cortisol secretion, increases bone formation, and plays an essential role in fertility.

Leptin crosses the blood-brain barrier via a transport mechanism and binds to specific receptors in certain brain regions.

Most leptin receptors are located in the body’s emotional center within the hypothalamus in the brain. Liver tissue and skeletal muscle also have corresponding receptors.

Leptin receptors occur in three isoforms. Among other functions, these are involved in the transport of leptin into the cerebrospinal fluid. Hypothalamic leptin receptors are involved in the regulation of feelings of hunger and satiety.

In addition, leptin receptors have been detected in other tissues, although their function remains unclear. The hypothalamic localization of the leptin receptor suggests an interaction with the satiety center.

Downstream neuropeptides in the hypothalamus include NPY and α-MSH: NPY increases appetite, while α-MSH (α-melanocyte-stimulating hormone) suppresses it. This results in a closed-loop regulatory system.

Stimulation of the Sympathetic Nervous System

Leptin also has a stimulating effect on the nervous system—more specifically, on the sympathetic nervous system—and, by decoupling cellular respiration from ATP synthesis, leads to an increase in blood pressure, heart rate, and thermogenesis.

Leptin Production

Since visceral body fat is the primary producer of leptin, its levels depend largely on the amount of fat stores present.

The fewer fat deposits, the less leptin circulates in the blood.

The lower the leptin levels, the greater the appetite.

The more fat deposits, the more leptin circulates in the blood.

The higher the leptin levels, the less appetite

Factors Affecting Leptin Levels

By the amount of body fat

Under balanced hormonal conditions in the body (homeostasis), people with a higher body fat percentage also have higher leptin levels than people with a lower body fat percentage. Under normal conditions, there is therefore a direct correlation here.

Reducing or increasing body fat percentage thus influences leptin levels.

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By reducing calorie intake

When calorie intake is reduced, the body responds by lowering leptin levels. Calorie intake is the second-most important regulator of serum leptin levels.

Reducing or increasing calorie intake thus affects leptin levels.

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Through the metabolic activity of fat cells

The metabolic activity of individual fat cells results in varying amounts of secreted leptin. Metabolically active visceral fat is the main producer

The formation and/or breakdown of visceral fat cells, in particular, can influence leptin production.

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Through the circadian rhythm

Under normal conditions, leptin is secreted at varying levels according to a specific daily rhythm. Elevated leptin levels are observed at night. This rhythm can be disrupted—for example, by shift work—and this disruption can affect all hormonal processes, including leptin.

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What are the effects of a decrease in leptin levels?

Under normal conditions

If the diet is isocaloric (tailored to individual needs) and body fat levels are “normal,” the brain receives a signal—via the binding of secreted leptin to leptin receptors in the brain—that food intake is sufficient.

In this case, the hormonal environment is conducive to fat burning, as no emergency situation is signaled.

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Calorie restriction

Reducing calories to a hypocaloric level (below requirements) causes leptin levels to drop rapidly. The brain receives a signal of starvation because not enough calories are being consumed. As a result, the body responds by lowering its metabolic rate.

This creates an environment conducive to fat storage.

Thyroid hormone levels drop, while the stress hormone cortisol rises, thereby promoting fat storage in the abdominal area. Stimulation of the production of the hormones ghrelin, neuropeptide Y (NPY), and anandamide leads to an increased feeling of hunger.

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Conclusion

The optimal condition for body fat loss would be a reduction in calorie intake combined with high leptin levels.

Is exogenous leptin supplementation effective?

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Oral Administration

Oral administration of exogenous leptin is not possible because leptin is a protein-based hormone.

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Leptin Administration via Injections for Obesity

Successful tests in mice have given scientists hope that obesity can also be successfully treated in humans.

Study

Leptin administration led to increased fat burning in obese mice, which occurred to a significantly greater extent than would have been possible through food deprivation alone. At the same time, energy expenditure increased.

Unfortunately, the test results cannot be applied to obese humans. The effects of leptin administration were too minimal in humans.

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Attempt at an Explanation – Disruption in the Leptin Regulatory Circuit – Leptin Resistance

The reason for the failed trial likely lies with the obese individuals themselves. Possible causes include a transport disorder at the blood-brain barrier or a defect in the signaling mechanism behind the leptin receptor (second messenger).

Leptin Resistance

It is likely that leptin resistance develops due to the elevated leptin levels commonly found in obese individuals (both non-diabetic and diabetic).

If, as is the case with insulin resistance, the receptors only bind leptin to a limited extent despite high leptin levels, no success can be expected from exogenous administration. Leptin receptors become desensitized over time as a result of poor dietary habits and high body fat levels.

In this case, therefore, treating obese individuals with leptin appears to be futile, since leptin resistance prevents the physiological effect of leptin on the target neurons.

Patients with an actual leptin deficiency might benefit from leptin replacement therapy.

Personally, I am not aware of any reports or empirical data regarding the use of exogenous leptin in competitive sports.

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Ways to Correct or Improve Leptin Resistance

Although difficult, it is not impossible to improve leptin resistance by changing dietary habits and reducing body weight. Studies have already observed a resensitization to leptin.

Leptin sensitivity at the receptor was also restored through increased physical activity. In studies, physically active individuals required less leptin to signal satiety to the brain.

Ways to Manipulate Endogenous Leptin Levels Through Diet

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Essential Facts

Leptin levels drop significantly after just one week of calorie restriction. However, it does not take nearly as long for leptin levels to return to baseline following a substantial increase in calorie intake. A rise in leptin levels becomes noticeable as early as 12–24 hours after increasing calorie intake. 

The Solution: Strategic Cheat Days

Cheat days with increased carbohydrate intake during a diet reset the body to a significantly higher rate of fat loss.

Why Carbohydrates?

Leptin, insulin, and carbohydrates are closely linked. The macronutrients fat and protein do not have the same effect on insulin levels as carbohydrates do. Therefore, an increased calorie intake from these two macronutrients will not have a comparable effect on leptin levels. To trigger a strong leptin response, larger amounts of carbohydrates must be consumed. In studies, leptin levels did not drop even under complete fasting conditions, as long as insulin and blood sugar levels were maintained through intravenous infusions.

An increased intake of carbohydrates on a “cheat day” therefore helps raise leptin levels, promoting renewed fat burning, and prevents a further drop in leptin levels, which would hinder fat loss.

Summary

We now know about leptin, a hormone that tells the brain how much body fat we have, to help it decide how to regulate our metabolism.

Depending on the reported leptin status, our brain responds by secreting certain hormones that either boost or slow down metabolism and also triggers feelings of hunger or satiety.

Through the targeted intake of calories and the proportion of body fat, we have the ability to control leptin levels ourselves and manipulate them for our own purposes—at least as long as the leptin regulatory loop is functioning properly.

In obesity, it is likely that this very regulatory loop has become unbalanced, and constantly high leptin levels have led to receptor resistance. In this case, fundamental lifestyle changes must be made to correct this imbalance.

With this post on leptin, I conclude my 3-part blog series and hope to have enriched all readers with new knowledge.

Until the next blog post.

Best regards

Yours,

Holger Gugg

www.body-coaches.de