Abstract:
Obesity is defined as a state of excess body fat responsible for increased body weight. It is a major health problem in several countries causing increased morbidity and mortality and high cost for the society. Obesity is a complex multifactorial disease with genetic and non-genetic interactions. Epigenetic transgenerational inheritance of obesity is an emerging new area of research where multiple environmental factors including endocrine-disrupting chemicals (EDCs), nutrition imbalance, and stress are involved. EDCs are a heterogenous group of exogenous chemicals or chemical mixtures that interfere with the action of hormones. A subset of these EDCs alters regulation of energy balance and weight control to favor weight gain and obesity by promoting adipogenesis and lipid accumulation. These EDCs are called obesogens. The exposed subjects are predisposed to weight gain despite normal diet and exercise. Obesogens can also cause resistance to weight loss in subjects on anti-obesity diet and/or drug. Interestingly, the obesity pandemic in humans coincides with the exponential increase in the number of EDCs/obesogens in the environment over the past few decades. The metabolic programming of obesity risk and its transgenerational inheritance can be linked to parental (both maternal and paternal) exposure to obesogens (e.g., bisphenol A, phthalates, tributyltin, nicotine, and monosodium glutamate), nutrition imbalance (e.g., undernutrition and high-fat diet), and stress. The epigenetic mechanisms include deoxyribonucleic acid methylation (the most studied mechanism), histone methylation, histone retention, chromatin structure alteration, and non-coding ribonucleic acids expression. Through epigenetic mechanisms affecting germ cells (egg or sperm), the environmental factors (e.g., obesogens, nutrition imbalance, and stress) directly influence genetic variation, inheritance, phenotypic variation, and adaptation. The heritable changes propagate through multiple generations without any new exposure to the initiating factor and increase obesity susceptibility. An adverse maternal exposure (F0 generation) can affect the fetus (F1 generation) and the germ cells of the fetus (F2 generation). With a direct exposure of the parents (F0 generation) and the fetus (F1 generation), the true transgenerational transmission is the F3 generation and beyond for the exposure of a pregnant female and the F2 generation and beyond for the exposure of a non-pregnant female or a male. A better understanding of the mechanisms of the transgenerational inheritance is critical for the implementation of preventive strategies in the fight against obesity pandemic. Although exposure to EDCs/obesogens and the resulting transgenerational inheritance of obesity cannot be entirely avoided in many situations, every effort should be made to minimize or avoid the exposure to obesogens, especially during the windows of sensitivity of the embryo/fetus.
