Daniela Sayuri Inoue*, Mohammad Fauzan Bin Maideen, Alberto Jiménez-Maldonado and Fábio Santos Lira*
Obesity is associated with an exacerbated synthesis and secretion of several molecules, which culminates in chronic low-grade inflammation and insulin resistance. Such conditions affect molecular and physiological responses of several organs and, if not resolved, predispose to the obese patients to suffer other diseases such as Type 2 diabetes, atherosclerosis, cancer, neural injuries, and cognitive impairments. A microenvironment with an excess of pro-inflammatory cytokines released by different cells, including immune and adipose cells lead to suffer metabolic and non-metabolic diseases during obesity. In this context, the role of neuronal guidance cues named netrin, semaphorin and ephrin is novel. Specifically, the available literature indicates that besides to their classic role as molecules that guide to the axon with its target site, the neuronal guidance cues exhibit immunomodulatory functions from adipose tissue to the neural environment. In the current narrative review, we discuss the participation of the neuronal guidance cues on the physiology and pathophysiology of obesity. We also discuss the feedback loop of the obesity on the netrin, semaphorin and ephrin functions that impair the structure and function of the brain. The integrative view of the neuronal guidance cues can be relevant to design new treatments focused to attenuate metabolic and immune disorders that suffering obese patients, and lead to them to acquire worse diseases such as Type 2 diabetes, atherosclerosis, cancer, and neural injuries.
cell adhesion, cell migration, UNC5B, neuropilins, Eph receptors, hippocampus
Exercise and Immunometabolism Research Group, Post-Graduation Program in Movement Sciences, Department of Physical Education, State University (Unesp), School of Technology and Sciences, Presidente Prudente,19060-900, São Paulo, The University of Sydney, School of Health Sciences, Faculty of Medicine and Health, NSW, Facultad de Deportes Campus Ensenada, Universidad Autónoma de Baja California, Exercise and Immunometabolism Research Group, Post-Graduation Program in Movement Sciences, Department of Physical Education, State University (Unesp), School of Technology and Sciences, Presidente Prudente,19060-900, São Paulo