Physiologist Manuel Tena-Sempere believes we will have medications to treat obesity some day

Obesity is a multifaceted disease with many contributing factors that require a comprehensive strategy to address. It’s even more difficult to treat in children and adolescents because its effects carry over into adulthood, deteriorating the quality of life and even leading to premature death. Various studies (Pasos 2022 and the European Childhood Obesity Surveillance Initiative) found that 20%-33% of minors are obese. Manuel Tena Sempere, a physiologist at the University of Córdoba (Spain), was recently awarded the Geoffrey Harris Prize by the European Society of Endocrinology for his research on one of the most complex mechanisms related to obesity: how the hypothalamus (the central brain region that controls body temperature, hunger, thirst and other functions) is related to obesity and adolescent development during puberty. His research team received €2.5 million ($2.74 million) from the European Research Council (ERC) to fund this research.

Question: What is the relationship between the hypothalamus, obesity and adolescent development?

Answer. Our project is analyzing the role of the hypothalamus in obesity that leads to pubertal alterations. The hypothalamus is a key area of the brain that regulates many processes, including maturation, the reproductive function and body weight control. We are studying the hypothalamus to discover the mechanisms that connect pubertal alterations with early-onset obesity. Genetic and experimental data show that obesity is probably a hypothalamic disease.

Early-onset obesity speeds up pubertal maturation, especially in females

Q. Does obesity favor extraordinary early development?

A. Early-onset obesity speeds up pubertal maturation, especially in females. Different epidemiological studies have revealed that girls with early-onset obesity also experience early puberty. This doesn’t mean that they have pathological precocious puberty, which is a disease, but that pubertal maturation, breast development and other characteristics begin months, even years earlier. The situation is less clear in children. Our project will also delve into explaining the differential characteristics of the impact of obesity on puberty in boys and girls.

Q. What are the consequences of early puberty?

A. Puberty is such an important maturational event that any alterations have immediate and long-term consequences. It can affect a person’s full height at maturity and psychological maturity, especially when there is a significant gap between physical and mental development. Various epidemiological studies have shown that it can also contribute to the development or perpetuation of diseases later in life, such as diabetes, obesity itself and even certain types of cancer. It can even lead to lower life expectancy. I don’t mean to be alarmist, but it’s important to know that alterations in puberty have long-term risks that we still don’t understand very well. We also don’t know much about the mechanisms of these changes, so it’s important to identify them.

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

Q. Can the hypothalamus be targeted?

A. Yes, some therapies can target brain circuits. But these therapies can have side effects, so they require very accurate strategies to target precise areas of the brain. There are drugs available to treat type 2 diabetes and obesity that can access and act on hypothalamic circuits. For example, the GLP1 analogues act at the peripheral level by modulating pancreatic insulin secretion, but they can also act on the brain.

Q. Are they safe?

A. They have relatively mild side effects and the therapeutic effects are very positive. But the fundamental problem in intervening or acting on complex hypothalamic circuits is that they overlap with each other. It’s very difficult to get precise molecules that do exactly what we want without producing other, less-desirable effects. Our research intends to clarify how these circuits work so we can define the most selective targets possible. We expect that this will lead to improved management of childhood obesity and pubertal alterations.

It’s very difficult to get precise molecules that do exactly what we want without producing other, less-desirable effects.

Q. Will we ever have a pill for obesity?

A. Semaglutide is a medication for weight loss and there is another drug that is still in clinical trials but should be on the market soon. Pharmacological treatments for obesity are possible, but obesity management is always complex and even more so in children. Pharmacological approaches to obesity alone are often doomed to failure. Other complementary actions are necessary, such as lifestyle changes. However, medications, combined with other therapies, including surgical interventions, can be very helpful.

Q. Can acting on the hypothalamus lead to eating disorders?

A. The important thing is to understand the circuits underlying a specific alteration so they can be selectively targeted. I think it’s possible to identify the components and circumstances that will truly help us manage obesity. The experimental evidence so far does not show that a pharmacological treatment can lead to an anorexic patient. Anorexia is a complex disease that is not primarily caused by alterations of the basic circuits that control energy balance, but is closely related to body perceptions. By using selective targeting, I believe it’s possible to ensure that therapies do not cross that red line or produce undesirable effects.

Q. Why is it so difficult to treat obesity?

A. Obesity is a pathological situation frequently conditioned by factors within the body that predispose an individual to overeat or consume less energy. Therefore, it’s not as simple as eating less because there are often underlying genetic and pathophysiological factors that lead to obesity. A comprehensive approach does not rely solely on a pill, but considers the entire therapeutic arsenal available to combat the complex problem of obesity.

Obesity is a pathological situation that is frequently conditioned by factors within the body that predispose an individual to overeat or consume less energy. Therefore, it’s not as simple as eating less.

Q. Is the problem big enough to be considered a pandemic?

A. Absolutely. The latest data shows that about 20% of all adolescents are obese, and an obese child is likely to remain obese after puberty and experience many significant health problems. We can honestly say there is an obesity pandemic and a childhood obesity pandemic because it’s a major health problem in many countries.

Q. What’s causing this obesity pandemic?

A. Societal changes leading to more sedentary lifestyles, especially in children. Also, nutritional and dietary patterns are not as healthy as they were a few decades ago. This leads to a greater propensity for obesity. Apart from that, there are also individual cases of morbid obesity with very specific causes, such as genetics.

Q. Does it affect girls and adolescents more?

A. It affects boys and girls equally, but the impacts of early-onset obesity on female and male puberty may be different, which is another area our project is studying. Although the basic mechanisms of puberty are similar in boys and girls, the regulation of these mechanisms varies by gender. It is important to analyze gender differences to provide personalized treatment for childhood obesity.

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

Q. Do lack of sleep and screen time have an effect?

A. They can be an additional risk factors. Sleep deprivation can lead to various kinds of metabolic disruption, including obesity. Likewise, more screen time implies a sedentary lifestyle with less physical activity, which also contributes to obesity. Obesity is essentially an imbalance between energy spent and ingested. If the energy we spend decreases and the energy we ingest increases, the excess is deposited in adipose tissue (body fat).

Q. When is a specialist needed?

A. An adult’s body mass index (BMI) is a good indicator. But BMI is not directly applicable to children, so it’s best to compare a child’s weight to the normal range for the age and gender. If the child’s weight deviates significantly from the norm, then the child may be overweight or obese. The pediatrician or pediatric endocrinologist diagnoses whether a child is overweight.

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