Leptin: the key to successful weight loss

The hormone leptin secreted by our fat tissue is supposed to reduce appetite. Obesity, however, makes the brain less sensitive to its signals, making it much harder to lose weight. How to get leptin under control?

Unlike us, our ancient ancestors did not have a constant food supply, but alternated periods of starvation with periods of relative abundance. It was therefore important for their survival that their bodies were able to adapt to this. One effective mechanism for this was the hormone leptin.

Leptin is a protein hormone secreted by several tissues in the body – these include the stomach lining, ovaries, breast gland tissue and skeletal muscles, but perhaps the most important is adipose tissue.

How to influence appetite?

There are also a relatively large number of functions that leptin has in the body. For example, it is related to reproduction, initiates the onset of puberty, regulates cardiovascular and immune functions, and also affects bone metabolism – its deficiency is a risk factor for osteoporosis, for example. But perhaps the most well-known function of leptin is the regulation of appetite.

As we have already described, adipose tissue is a very important producer of leptin. As a result, the more of it there is in the body, the more leptin it produces. Subsequently, this hormone binds to a receptor in a part of the brain called the hypothalamus, which is the signal for a reduction in appetite. This is basically the fat cells saying to the brain, “We’re fed up, you can reduce your food intake”.

Perhaps everyone at this point thinks, “Aha! Why do obese people overeat, their fat tissue must produce buckets of leptin!” The objection is not only logical, but also true; obese people actually produce much more leptin than lean ones. But the problem is that at the same time as obesity, the body develops what is called leptin resistance. This is because there is a disruption in what is called cell signalling, a complex of biochemical reactions by which, in simple terms, the cell receives instructions from its environment on how to behave. Thus, fat cells can produce leptin as if they were a race, but the body has lost its sensitivity to it and there is no reduction in appetite.

What do genes decide?

The emergence of leptin resistance is mainly related to a mechanism called gene methylation. It is a so-called epigenetic reaction that can completely switch off, i.e. completely disable the function, of some genes in our DNA. In fact, obesity is one of the significant factors that negatively affect the rate of methylation of our genes. It is because of this that it increases the risk of a number of serious diseases, but it also affects the body’s response to leptin.

In many cases, the problem arises already during intrauterine development. The cause here is usually hyperglycaemia (high blood sugar in the mother’s blood), which is particularly typical of gestational diabetes. Maternal hyperglycaemia alters the methylation patterns of the baby, which in turn affect the production of placental leptin. Thus, children of mothers who suffer from hyperglycaemia in pregnancy have an increased risk of both diabetes and obesity in later life.

Another risk factor in pregnancy that increases a child’s risk of obesity is malnutrition, specifically low protein intake. This will cause epigenetic changes in the child that will increase the risk of weight gain later in life if a high-energy diet is consumed.

How to influence leptin production

However, we influence the production of the hormone leptin and the brain’s sensitivity to its signals throughout our lives. In particular, factors that have a generally bad influence on our epigenome, i.e. on chemical reactions that adversely affect the activity of our genes, have a negative impact.

Some research also suggests that leptin production may be reduced not only by a high-energy diet with excessive saturated fat consumption, but also by high fructose consumption. This carbohydrate is widely used in industrial food production, especially in the form of glucose-fructose syrup, which is cheaper than conventional sugar. The massive use of this sweetener may thus be contributing to the global obesity epidemic.

Moreover, leptin production is very closely related to the circadian clock. It is very likely that a disruption of the circadian clock will negatively affect leptin production and thus the tendency to obesity. The problem here is not only the disruption of the sleep rhythm itself, for example in people working night shifts, but also the consumption of food at unnatural hours, especially late in the evening and at night. In one study, for example, mice were fed a high-fat diet, with one group receiving food at normal times of the day and the other at night. The night eaters gained weight two and a half times faster than the other group! Similar, though not as striking, results were also found in studies of human volunteers.

Overeating in general also leads to the development of leptin resistance – if a person has overeaten at any time in their life, it is likely that they have developed leptin resistance. Moreover, this information puts the often-used practice of starting weight loss diets with short-term fasting in a completely different light. After just twelve hours without food, the body’s response to leptin begins to return to normal.

For women, the critical moment for the onset of overweight is the menopause. This is not only due to a slowing metabolism, the intensity of which generally decreases with age, but also leptin. If the body is deficient in estrogen, the brain’s sensitivity to leptin decreases.

The road to a slim figure

In addition, epigenetics plays a role not only in the development of excess weight, but also in the effort to get rid of excess kilograms. In fact, most epigenetic reactions are reversible, so we can influence the activity of our genes to work in our favour again.

For example, people who had lower levels of methylation of the TNF promoter responded much better to dietary modification in studies – they lost more weight after restricting calorie intake than those with high levels of methylation at this DNA site.

Epigenetically, the gene by which leptin itself is produced can also be directly influenced. Its methylation increases in people who consume a high-fat diet. This results in overall lower leptin levels and therefore weight gain.

Unfortunately, these changes are also hereditary, so it is true that our tendency to obesity can be caused by the way our parents ate before we were conceived. For example, it has been shown that if a father eats a diet rich in fat and energy, this causes epigenetic changes in his leptin gene that are then passed on to his offspring. They are then more prone to weight gain. This completes the circle.

Useful dietary supplements

Certain nutrients commonly found in our diet have strong epigenetic effects. If we take them in higher concentrations, we will not only support our health but also our efforts to lose excess weight.

Omega-3s – these unsaturated fatty acids generally have a positive effect on the methylation levels of our genes, and according to research, they are also able to affect the methylation of the leptin gene. They have also been shown to have a general effect on promoting adipose tissue loss. In addition, they can eliminate the negative epigenetic changes caused by a high-fat diet.

Curcumin – this substance has been fairly well researched in terms of its effect on obesity. It works positively through several mechanisms, and the effect on leptin is one of them. Overall, it promotes its production and also helps to reduce leptin resistance (and insulin resistance, which is important in both obesity and diabetes). In experiments on mice, there was even an increase in leptin production and a decrease in leptin resistance in individuals who were fed a high-fat or high-fructose diet. For greater effectiveness, curcumin should be taken together with piperine.

Resveratrol – a dye contained mainly in red wine combines epigenetic action with the fact that it is a phytoestrogen, a substance similar in composition and action to the female sex hormone estrogen. This helps to balance its levels during the menopause and thus prevents a decrease in sensitivity to leptin.

EGCG – epigallocatechin gallate from green tea has somewhat paradoxical effects on leptin production. Most studies have confirmed a reduction in leptin levels when it is used, however, in virtually all the subjects studied there was no increase in appetite, as would be logical, but rather a reduction in appetite and subsequent weight loss.