Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases.

María Teresa Flores-Dorantes,Ruth Gutiérrez-Aguilar,Yael Efren Díaz-López

doi:10.3389/fnins.2020.00863

Abstract

Obesity is a multifactorial disease in which environmental conditions and several genes play an important role in the development of this disease. Obesity is associated with neurodegenerative diseases (Alzheimer, Parkinson, and Huntington diseases) and with neurodevelopmental diseases (autism disorder, schizophrenia, and fragile X syndrome). Some of the environmental conditions that lead to obesity are physical activity, alcohol consumption, socioeconomic status, parent feeding behavior, and diet. Interestingly, some of these environmental conditions are shared with neurodegenerative and neurodevelopmental diseases. Obesity impairs neurodevelopment abilities as memory and fine-motor skills. Moreover, maternal obesity affects the cognitive function and mental health of the offspring. The common biological mechanisms involved in obesity and neurodegenerative/neurodevelopmental diseases are insulin resistance, pro-inflammatory cytokines, and oxidative damage, among others, leading to impaired brain development or cell death. Obesogenic environmental conditions are not the only factors that influence neurodegenerative and neurodevelopmental diseases. In fact, several genes implicated in the leptin–melanocortin pathway (LEP, LEPR, POMC, BDNF, MC4R, PCSK1, SIM1, BDNF, TrkB, etc.) are associated with obesity and neurodegenerative and neurodevelopmental diseases. Moreover, in the last decades, the discovery of new genes associated with obesity (FTO, NRXN3, NPC1, NEGR1, MTCH2, GNPDA2, among others) and with neurodegenerative or neurodevelopmental diseases (APOE, CD38, SIRT1, TNFα, PAI-1, TREM2, SYT4, FMR1, TET3, among others) had opened new pathways to comprehend the common mechanisms involved in these diseases. In conclusion, the obesogenic environmental conditions, the genes, and the interaction gene–environment would lead to a better understanding of the etiology of these diseases.

Highlights

Obesity is an excess of fat body mass that may decrement health
We will briefly describe the genes involved in this pathway and that have been associated with monogenic obesity, as well as their effect in developing neurodegenerative diseases (NDgDs) and neurodevelopmental diseases (NDvDs) (Table 1)
We addressed the obesogenic environmental conditions that influence the development of NDgD or NDvD

Summary

INTRODUCTION

Obesity is an excess of fat body mass that may decrement health. Obesity is caused by an energy imbalance due to an excess of food intake and less physical activity. More than 130 lifestyle factors, such as socioeconomic status, general health, mental health, sleep, physical activity, alcohol consumption, smoking, diet, the genetic risk score (GRS), among others, were analyzed to study the interaction between gene and environment leading to obesity. Maternal obesity increases the risk for intellectual disability in 1.3–3.6-fold, ADHD in 1.6–2.8-fold, and 2-fold in the difficulty of regulating emotions (Edlow, 2017) Another NDvD is SCZ; its risk factors to develop it include obesity, poor diet, physical activity, genetic vulnerability, stress, environmental toxins, among others (Debnath et al, 2015). We will briefly describe the genes involved in this pathway and that have been associated with monogenic obesity, as well as their effect in developing NDgD and NDvD (Table 1) These genes are LEP, LEPR, POMC, CART, NPY, MC4R, PCSK1, SIM1, BDNF, and TrKB. This model exhibited plaque and tangle pathology, synaptic dysfunction, and showed amyloid

Findings

DISCUSSION

CONCLUSION