Manuel Tena-Sempere, physiologist: "Pharmacological treatments for obesity are possible"

Obesity is a polyhedral disease with many factors that requires a complex strategy.

In the case of children and adolescents, an aggravating circumstance is added: its effects carry over into adulthood and its consequences shorten life or make it worse.

Between 20% and 33% of minors, according to different studies (Pasos 2022 or Childhood Obesity Surveillance Initiative) suffer from it.

Manuel Tena Sempere, a 53-year-old Cordovan professor of Physiology at the university in his hometown and recently recognized with the Geoffrey Harris Award from the European Society of Endocrinology, tries to unravel one of the most complex mechanisms related to being overweight: how the hypothalamus , the central area of ​​the brain that controls body temperature, hunger or thirst, among other functions,

It is related to overweight and early pubertal maturation.

His research group has received the endorsement of the European Research Council (ERC), which has granted him an exclusive grant of 2.5 million euros to unveil this mechanism.

Ask.

What is the relationship of the hypothalamus, overweight and maturation?

Answer.

Our project attempts to assess the role of the hypothalamus in the connection between obesity and pubertal disturbances.

The hypothalamus is a fundamental brain area in the regulation of many processes that include both maturation and reproductive function as well as control of body weight.

We searched this center that integrates reproductive functions, metabolism control and body weight to unravel what are the mechanisms that connect pubertal alterations with early-onset obesity.

Genetic and experimental data suggest that obesity is probably a hypothalamic disease.

Early-onset obesity tends to accelerate pubertal maturation, especially in females

Q.

Does obesity promote extraordinary early development?

A.

Early-onset obesity tends to accelerate pubertal maturation, especially in females.

Different epidemiological studies in girls have clearly shown that, in those who suffer from early obesity, the age of onset of puberty is also accelerated.

It does not necessarily mean that they fall within the range of pathological precocious puberty, which is a disease, but it does mean that an acceleration occurs which, above all, causes the onset of pubertal maturation, breast development and other characteristics to take place months , even years, before what was happening.

In children, the situation is not so clear.

Our project also intends to delve into trying to explain the differential characteristics of the impact of obesity on puberty in boys and girls.

Q.

What are the consequences of this early pubertal maturation?

R.

.

Puberty is such an important maturational event that the consequences of its alterations are both immediate and long-term.

It can affect or alter the final height or psychological maturation, especially when there is a significant discrepancy between physical and mental development.

Different epidemiological studies have also revealed that it can contribute to the development or perpetuation of diseases in later stages of life, such as diabetes, obesity itself and even certain types of cancer.

It can even mean a decrease in life expectancy in the long term.

It is not a question of being alarmist, but it is necessary to know that, when there are alterations of puberty, there is a long-term risk that we still do not know very well,

The alteration of puberty can contribute to the development or perpetuation of diseases in later stages of life, such as diabetes, obesity itself and even certain types of cancer.

Q.

Can you influence the hypothalamus?

A.

Yes it is possible.

There are some therapies that are directed at brain circuits.

But, obviously, there is a risk of possible added effects to those that are initially pursued and requires the design of very precise strategies that are directed at the specific target that you want to hit.

There are drugs currently on the market for the treatment of type 2 diabetes, and more recently, obesity, whose mechanism of action is partly derived from the ability to access and act on hypothalamic circuits.

This is the case of GLP1 analogues, which act at the peripheral level, modulating pancreatic insulin secretion, but they can also act at the brain level.

Q.

Is it safe?

R.

Its side effects are relatively moderate and the therapeutic ones are very positive.

But the fundamental problem when it comes to interfering with or acting on the hypothalamic circuits is that they are complex and the processes overlap with each other.

It's very hard to get molecules precise enough to do exactly what we want without doing just what might be less useful.

Our project tries to better understand how these circuits work to try to define the most selective target possible and that, eventually, in the future, can help to better manage childhood obesity or pubertal disorders, so that the knowledge we generate can be useful to understand the underlying mechanisms and to be applicable in the field of human health.

It's very hard to get molecules precise enough to do exactly what we want without doing just what might be less useful.

Q.

Will there be a pill against obesity?

A.

Semaglutide is one example and there is another, more recent drug that is still in the experimental phase and will be on the market soon.

Pharmacological treatments against obesity are possible, but, obviously, its management is always complex and, if we talk about childhood obesity, even more so.

The exclusively pharmacological approach to obesity is doomed to failure on many occasions.

Other angles of action are necessary, such as changes in lifestyles.

But, drug therapy and others, such as surgery, can obviously be a great help.

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Q.

Can acting on the hypothalamus lead to eating disorders?

R.

The important thing is to try to know well the circuits that underlie a certain alteration to be able to act on them in the most selective way possible.

With this premise, I believe that it is possible to separate the really interesting components or circumstances for the management of obesity.

The experimental evidence to date does not seem to suggest that a drug treatment can lead to an anorexic patient, for example.

Anorexia is a complex disease that does not derive mainly from the alteration of the basic circuits that control energy balance, but rather has a component related to the perception of one's own body.

If it is targeted in a selective way, I believe that it is possible to ensure that the therapies do not cross that red line or produce undesirable effects.

It is something that currently

Q.

Why is it so difficult to treat obesity?

A.

Obesity is a pathological situation that, on many occasions, is conditioned by endogenous alterations that predispose the individual to overeat or consume less energy.

For this reason, it is not as simple as eating less because there is often a genetic and pathophysiological substrate that leads to obesity.

The ideal is a comprehensive approach that does not reside only in a pill, but that considers the entire therapeutic arsenal that we can generate to combat a problem as big as obesity.

This comprehensive approach is the main objective of the Biomedical Research Center on Obesity and Nutrition Network (CIBEROBN), of the Carlos III Health Institute, of which our group from the University of Córdoba is also a part.

Obesity is a pathological situation that, on many occasions, is conditioned by alterations that predispose the individual to overeat or consume less energy.

It is not as simple as eating less

Q.

Is the problem big enough to be considered a pandemic?

A.

Totally.

The most recent figures suggest that approximately 20% of all adolescents are obese.

And an obese child is very likely to remain so after puberty and lead to a whole series of very considerable health problems.

Honestly, talking about an obesity pandemic or a childhood obesity pandemic is correct because, in addition, it is a generalized situation that affects many countries with a very high frequency.

It is really a health problem of the first order.

Q.

Why has this high incidence been generated?

A.

Fundamentally, due to the change in the general lifestyle of society, which leads to a greater sedentary lifestyle, especially in the child population, and to nutrition or eating patterns that may not be as healthy as a few decades ago.

This leads to a greater propensity to develop obesity, also in the child population.

Besides, there are also specific individual cases of morbid obesity with very specific causes, such as genetics.

Q.

Does it affect girls and adolescents more?

A.

It affects both boys and girls, but the impact of early-onset obesity on female and male puberty may be different, as we intend to address in our project.

It is clear that, although the basic mechanisms of puberty are similar in boys and girls, the regulation of these mechanisms varies according to gender and, consequently, it is important to also consider or analyze these sexual differences to try to address them in a personalized way. the problem of childhood obesity.

Although the basic mechanisms of puberty are similar in boys and girls, their regulation varies by gender.

Q.

Does lack of sleep and the use of screens affect?

A.

Sleep deprivation can lead to metabolic disturbances of various kinds, including obesity.

It may be an additional risk factor.

In the same sense, greater exposure to screens implies greater sedentary lifestyle and less physical activity contributes.

In the end, obesity is a disturbance in the balance between the amount of energy we ingest and the amount we consume.

If the amount of energy we consume decreases and the amount of energy we take in increases, the result is an excess that is deposited in adipose tissue.

Q.

When do you have to see a specialist?

A.

In adults, the body mass index is used, which in the child population is not directly applied because it has distortions, so it is established based on the comparison with what would be the normality of the population.

If there is a deviation of a certain magnitude with respect to that normality, it can be said if the child is overweight or obese.

The pediatrician or pediatric endocrinologist must accurately assess whether or not you are overweight.

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