333
selection of food results in the alteration of basal metabolism or the energy equilibrium to favor reserve calories. Last but not least, alterations in endocrine tissues
including liver, brain, pancreas, adipose tissue, or gastrointestinal tract which alters
insulin sensitivity and lipid metabolism also may have involvement.
Genetically, obesogens work just by regulating nuclear transcriptional factors
that further regulate lipid change and/or adipocyte differentiation/multiplication,
such as PPARα, PPAR-δ, and PPAR-γ (peroxisome proliferator-activated receptors)
and steroid hormone receptors. After binding to ligands these receptors work as
ligand-activated transcription factors, which with the help of response elements
binds to DNA and regulates precise patterns of gene expression [66].
Parental Exposure and Early Childhood Obesity
There are multiple reasons for childhood obesity, starting from the individual level
such as behavioral risk aspects including high fat consumption, working behavior,
and time duration, and societal-level risk aspects which determine diet and physical
activity such as agricultural policies, suburbanization, and mechanization [67–69].
However, there is an interesting emerging theory which states that exposure in early
life (4–10 years) to environmental endocrine disruptors has a crucial role in altering
metabolic programming that causes obesity. Prenatal exposure to enclosed PAHs
environment showed to have high BMI z score which suggests obesity at the age of
5 and fat mass at the age of 7 years. The effect due to PAHs when exposed in prenatal life on fetal body size is due to the addition of fat mass without any alteration in
lean mass. Pregnant women kept in controlled environment monitored for PAH
exposure, 21% and 25% at age 5 and 7 years, respectively, were found obsessed
[70]. Obesogens (endocrine-disrupting chemicals) promote adipogenesis that
causes weight gain [71].
Mechanism of Toxicity of PAHs
PAH toxicity was initially investigated by John Hill in 1761, a known medical practitioner who in tobacco snuff consumers founded nasal cancer in a high incidence
rate [72]. Low-molecular weight PAHs (composed of two or three aromatic rings)
showed acute toxicity, while high molecular weight PAHs (four or more rings) are
found to be genotoxic [73, 74]. It has been verified that PAHs bind covalently to
DNA, RNA, and proteins, but the carcinogenicity lies in the covalent interaction of
PAHs to DNA only [5, 75]. Moreover, the toxicity of daughter products is more
compared with parent PAHs which can result in critical cellular effects [76].
Monooxygenase group of enzymes in humans cytochrome P450 (as discussed
above in detail) converts PAHs to epoxides, some of which (like “bay-region” diol
epoxides) have high reactivity and is named as crucial carcinogens. Such epoxides
19 Role of Polycyclic Aromatic Hydrocarbons as EDCs in Metabolic Disorders
selection of food results in the alteration of basal metabolism or the energy equilibrium to favor reserve calories. Last but not least, alterations in endocrine tissues
including liver, brain, pancreas, adipose tissue, or gastrointestinal tract which alters
insulin sensitivity and lipid metabolism also may have involvement.
Genetically, obesogens work just by regulating nuclear transcriptional factors
that further regulate lipid change and/or adipocyte differentiation/multiplication,
such as PPARα, PPAR-δ, and PPAR-γ (peroxisome proliferator-activated receptors)
and steroid hormone receptors. After binding to ligands these receptors work as
ligand-activated transcription factors, which with the help of response elements
binds to DNA and regulates precise patterns of gene expression [66].
Parental Exposure and Early Childhood Obesity
There are multiple reasons for childhood obesity, starting from the individual level
such as behavioral risk aspects including high fat consumption, working behavior,
and time duration, and societal-level risk aspects which determine diet and physical
activity such as agricultural policies, suburbanization, and mechanization [67–69].
However, there is an interesting emerging theory which states that exposure in early
life (4–10 years) to environmental endocrine disruptors has a crucial role in altering
metabolic programming that causes obesity. Prenatal exposure to enclosed PAHs
environment showed to have high BMI z score which suggests obesity at the age of
5 and fat mass at the age of 7 years. The effect due to PAHs when exposed in prenatal life on fetal body size is due to the addition of fat mass without any alteration in
lean mass. Pregnant women kept in controlled environment monitored for PAH
exposure, 21% and 25% at age 5 and 7 years, respectively, were found obsessed
[70]. Obesogens (endocrine-disrupting chemicals) promote adipogenesis that
causes weight gain [71].
Mechanism of Toxicity of PAHs
PAH toxicity was initially investigated by John Hill in 1761, a known medical practitioner who in tobacco snuff consumers founded nasal cancer in a high incidence
rate [72]. Low-molecular weight PAHs (composed of two or three aromatic rings)
showed acute toxicity, while high molecular weight PAHs (four or more rings) are
found to be genotoxic [73, 74]. It has been verified that PAHs bind covalently to
DNA, RNA, and proteins, but the carcinogenicity lies in the covalent interaction of
PAHs to DNA only [5, 75]. Moreover, the toxicity of daughter products is more
compared with parent PAHs which can result in critical cellular effects [76].
Monooxygenase group of enzymes in humans cytochrome P450 (as discussed
above in detail) converts PAHs to epoxides, some of which (like “bay-region” diol
epoxides) have high reactivity and is named as crucial carcinogens. Such epoxides
19 Role of Polycyclic Aromatic Hydrocarbons as EDCs in Metabolic Disorders