Title:Role of Neuronal Guidance Cues in the Pathophysiology of Obesity: A Peripheral and Central Overview
Volume: 27
Issue: 21
Author(s): Daniela S. Inoue*, Mohammad F. Bin Maideen, Alberto Jiménez-Maldonado and Fábio S. Lira*
Affiliation:
- Post-Graduation Program in Movement Sciences, Department of Physical Education, State University (Unesp), School of Technology and Sciences, Presidente Prudente, 19060-900, São Paulo,Brazil
- Post-Graduation Program in Movement Sciences, Department of Physical Education, State University (Unesp), School of Technology and Sciences, Presidente Prudente, 19060-900, São Paulo,Brazil
Keywords:
Cell adhesion, cell migration, UNC5B, neuropilins, Eph receptors, hippocampus.
Abstract: 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 the obese patients to 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
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 their classic
role as molecules that guide the axon to 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 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 in designing new treatments focus
on attenuating metabolic and immune disorders in obese patients and reduce the risk of acquiring diseases
such as Type 2 diabetes, atherosclerosis, cancer, and neural injuries.