NGF and Its Role in Immunoendocrine Communication during Metabolic Syndrome

Abstract

Nerve growth factor (NGF) was the first neurotrophin described. This neurotrophin contributes to organogenesis by promoting sensory innervation and angiogenesis in the endocrine and immune systems. Neuronal and non-neuronal cells produce and secrete NGF, and several cell types throughout the body express the high-affinity neurotrophin receptor TrkA and the low-affinity receptor p75NTR. NGF is essential for glucose-stimulated insulin secretion and the complete development of pancreatic islets. Plus, this factor is involved in regulating lipolysis and thermogenesis in adipose tissue. Immune cells produce and respond to NGF, modulating their inflammatory phenotype and the secretion of cytokines, contributing to insulin resistance and metabolic homeostasis. This neurotrophin regulates the synthesis of gonadal steroid hormones, which ultimately participate in the metabolic homeostasis of other tissues. Therefore, we propose that this neurotrophin’s imbalance in concentrations and signaling during metabolic syndrome contribute to its pathophysiology. In the present work, we describe the multiple roles of NGF in immunoendocrine organs that are important in metabolic homeostasis and related to the pathophysiology of metabolic syndrome.

Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns

“…Within migratory neural crest cells, NT-3’s mitotic effect suggests that it is involved in gangliogenesis, while it exhibits autocrine and/or paracrine actions needed for the proliferation, differentiation, and survival of sympathetic neuroblasts [ 47 ]. The presence of the NT-3 transcript and protein in the physiological and pathological placenta throughout pregnancy has been confirmed in a study which investigated the presence of this molecule in placental specimens of normal pregnancies and pregnancies complicated by preeclampsia and chorioamnionitis [ 54 ]. In our small cohort study, there were only two cases complicated by gestational hypertension, one case from the AGA group who also developed gestational diabetes and another case from the LGA group.…”

“…Thus, pathophysiological links between NGF levels and development of MS may begin during fetal life, particularly since it is thought that NGF regulates certain pathways possibly leading to MS development. However, there is at present a lack of integrative data on the manifold roles of this neurotrophin within tissues involved in the immunoendocrine axis as well as on whether disruption of these might induce development of MS [ 54 ]. In mammals, pancreatic β-cells are the only cells that synthesize and secrete NGF and insulin.…”

Plasma-free metanephrines, nerve growth factor, and renalase significance in patients with PCOS

“…However, the sympathetic system is not a significant modulator of the NGF release in fat mass, unlike ovaries [ 50 ]. NGF secretion has been studied in patients with obesity and metabolic disturbances, but the results are somewhat contradictory [ 54 – 56 ]. Chronic sympathetic nervous system overactivity is a well-known factor linking adiposity, insulin resistance, and metabolic abnormalities [ 57 ].…”

Single-cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia

“…Interestingly, changes in systemic and local 58 level of NGF have been reported to closely relate to insulin resistance and diabetes. 59 Moreover, blunted mTOR signaling in AT can lead to insulin resistance. 43 , 60 Taken together, future investigations will assess protective roles of the NGF/CD271/mTOR axis in AT against insulin resistance.…”