152
and overweight children globally rose from 32 million in 1990 to 41 million in
2016. Childhood obesity has vulnerable long-term effects on the overall health.
Obese children are more prone to develop respiratory problems, hypertension, cardiovascular diseases, insulin resistance, psychological disturbances, and fracture
risks in later life [21].
Potential Obesogenic Mechanism of Endocrine Disrupting
Chemicals
Several mechanisms have been hypothesized to explain the consequences of EDCs
on early life obesity. It includes (a) mitochondrial dysfunction and oxidative stress,
(b) peroxisome proliferator-activated receptor gamma (PPARγ), (c) epigenetic
mechanism (DNA methylation), and (d) estrogen receptor [22].
Mitochondrial Dysfunction and Oxidative Stress
Mitochondrial dysfunction is one of the keystones in the development of obesity
due to continuous exposure to EDCs. Through an enhanced aggregation of diacylglycerols and reactive oxygen species (ROS) mainly in insulin resistant tissues such
as hepatocytes, the mitochondrial dysfunction contributes to obesity [23]. Multiple
studies revealed obesity and insulin resistance in mice when exposed to PCBs due
to impairment in mitochondria and adipokines level [24, 25]. Oxidative stress due
to EDCs also contributes to increase in weight through lipid peroxidation and adipocyte differentiation [26]. Furthermore, the ROS accelerates the PPARγ transcription resulting in enhanced adipogenesis [27].
Peroxisome Proliferator-Activated Receptor Gamma
PPARγ is an important nuclear receptor in the initiation of adipogenesis. PPARγ is
responsible for the differentiation of adipocytes, lipid metabolism, and energy balance [28]. Upon activation, PPARγ activates genes that enhance fat storage and
suppress lipid metabolism genes [29]. These receptors have special binding pockets
that are capable of interacting with extrinsic substances [30]. EDCs, especially
mono 2-ethyl-hexyl phthalate activates numerous PPARγ target genes and induces
adipogenesis [31]. BPA induces adipogenesis through PPARγ mechanism. It travels
across from mother to fetus through the placental barrier. And accelerates the transcription of adipocyte genes through directly effecting PPARγ1 and PPARγ2 cell
cycle transcriptional factors [32].
T. H. Mallhi et al.
and overweight children globally rose from 32 million in 1990 to 41 million in
2016. Childhood obesity has vulnerable long-term effects on the overall health.
Obese children are more prone to develop respiratory problems, hypertension, cardiovascular diseases, insulin resistance, psychological disturbances, and fracture
risks in later life [21].
Potential Obesogenic Mechanism of Endocrine Disrupting
Chemicals
Several mechanisms have been hypothesized to explain the consequences of EDCs
on early life obesity. It includes (a) mitochondrial dysfunction and oxidative stress,
(b) peroxisome proliferator-activated receptor gamma (PPARγ), (c) epigenetic
mechanism (DNA methylation), and (d) estrogen receptor [22].
Mitochondrial Dysfunction and Oxidative Stress
Mitochondrial dysfunction is one of the keystones in the development of obesity
due to continuous exposure to EDCs. Through an enhanced aggregation of diacylglycerols and reactive oxygen species (ROS) mainly in insulin resistant tissues such
as hepatocytes, the mitochondrial dysfunction contributes to obesity [23]. Multiple
studies revealed obesity and insulin resistance in mice when exposed to PCBs due
to impairment in mitochondria and adipokines level [24, 25]. Oxidative stress due
to EDCs also contributes to increase in weight through lipid peroxidation and adipocyte differentiation [26]. Furthermore, the ROS accelerates the PPARγ transcription resulting in enhanced adipogenesis [27].
Peroxisome Proliferator-Activated Receptor Gamma
PPARγ is an important nuclear receptor in the initiation of adipogenesis. PPARγ is
responsible for the differentiation of adipocytes, lipid metabolism, and energy balance [28]. Upon activation, PPARγ activates genes that enhance fat storage and
suppress lipid metabolism genes [29]. These receptors have special binding pockets
that are capable of interacting with extrinsic substances [30]. EDCs, especially
mono 2-ethyl-hexyl phthalate activates numerous PPARγ target genes and induces
adipogenesis [31]. BPA induces adipogenesis through PPARγ mechanism. It travels
across from mother to fetus through the placental barrier. And accelerates the transcription of adipocyte genes through directly effecting PPARγ1 and PPARγ2 cell
cycle transcriptional factors [32].
T. H. Mallhi et al.