In a study in mice, a team of Spanish researchers has identified some of the mechanisms of the nervous system involved in the metabolic control of puberty and its alterations associated with anorexia and obesity.
Puberty is a critical stage of development during which physical and psychological changes. Multiple factors cooperate in this process, including genetic inheritance, environmental factors and the metabolic and nutritional status of the organism.
In a new study carried out in mice, researchers from the Maimónides Institute of Biomedical Research (IMIBIC), the University of Córdoba (UCO) and the Center for Biomedical research in Network for Physiopathology of Obesity and Nutrition (CIBEROBN), led by Professor Manuel Tena-Sempere, have demonstrated that negative energy balance caused by poor nutrition activates an energy sensor called AMPK.
This effect is produced by a suppressed production of kisspeptins, brain molecules that activate the reproductive system and that are essential for puberty to begin at an appropriate age.
Kiss1 neurons, identified in the different species of mammals including humans, play an essential role in the central regulation of the functioning of the reproductive system and of puberty. Such is its importance, that mutations that inactivate the Kiss1 gene produce infertility and absence of puberty in humans and other species. Previous work by Dr. Tena-Sempere’s group showed that the activity of Kiss1 neurons is influenced by metabolic factors.
In relation to the metabolic and nutritional control of puberty, a very remarkable increase of metabolic disorders in the pediatric population has been detected worldwide in the last years. These include alarming problems as increasing rates of childhood obesity and higher frequency of eating disorders, such as anorexia or bulimia. As a consequence, the scientific community has paid special attention not only to the study of their causes, but also of the consequences derived from these early onset metabolic disorders.
Anorexia delays puberty
Among these consequences, researchers have found a close connection between the increase in the incidence of early metabolic diseases and alterations in the age of arrival of puberty, especially in girls. Thus, while conditions of excess in energy reserves, such as obesity, are related to earlier arrival of puberty; conditions caused by caloric deficit, such as anorexia, are associated with its delay.
Although, a priori, it might seem that these alterations in the age of puberty do not pose a serious health problem, recent studies have shown that this phenomenon can have a negative impact on health in later stages of development. An association of these pubertal alterations has been described with an increased risk of suffering cardiometabolic diseases (such as hypertension, obesity and diabetes), breast cancer, behavioral disorders, short stature and even a shorter life expectancy.
However, the mechanisms through which metabolic signals interact with the reproductive axis in situations of altered puberty associated with metabolic pathologies are not yet known precisely. The work that is now published helps to elucidate some of the factors involved in this phenomenon.
The data open a window to the possible utility of AMPK as a pharmacological target for the treatment of pubertal disorders, especially those of metabolic origin. Several drugs used clinically, such as metformin, act by modulating AMPK activity.