Obesity as a Neuroendocrine Reprogramming

Obesity represents a health problem resulting from a broken balance between energy intake and energy expenditure leading to excess fat accumulation. Elucidating molecular and cellular pathways beyond the establishment of obesity remains the main challenge facing the progress in understanding obesity and developing its treatment. Within this context, this opinion presents obesity as a reprogrammer of selected neurological and endocrine patterns in order to adapt to the new metabolic imbalance represented by obesity status. Indeed, during obesity development, the energy balance is shifted towards increased energy storage, mainly but not only, in adipose tissues. These new metabolic patterns that obesity represents require changes at different cellular and metabolic levels under the control of the neuroendocrine systems through different regulatory signals. Therefore, there are neuroendocrine changes involving diverse mechanisms, such as neuroplasticity and hormonal sensitivity, and, thus, the modifications in the neuroendocrine systems in terms of metabolic functions fit with the changes accompanying the obesity-induced metabolic phenotype. Such endocrine reprogramming can explain why it is challenging to lose weight once obesity is established, because it would mean to go against new endogenous metabolic references resulting from a new "setting" of energy metabolism-related neuroendocrine regulation. Investigating the concepts surrounding the classification of obesity as a neuroendocrine reprogrammer could optimize our understanding of the underlying mechanisms and, importantly, reveal some of the mysteries surrounding the molecular pathogenesis of obesity, as well as focusing the pharmacological search for antiobesity therapies on both neurobiology synaptic plasticity and hormonal interaction sensitivity.