Affiliation:
1. Main Line Health System,
Wynnewood, PA, USA
2. Emeritus Professor, University of Pennsylvania, Perlman School of Medicine, Philadelphia,
PA, USA
3. Department of Internal Medicine, Lankenau Medical Center, Wynnewood, PA, USA
Abstract
Abstract:
The incidence of metabolic disorders, such as obesity and type two diabetes (T2DM),
continues to increase worldwide, and their onset is often attributed to adherence to a western diet
and a sedentary lifestyle. However, large variability exists in one's likelihood of developing metabolic
dysregulation, illustrating that our understanding of heritability patterns remains poorly understood.
Diabetes and obesity are multifactorial diseases, and their onset is influenced by both genetic
and environmental factors. Genome-wide association studies report a number of alterations in
the coding sequence associated with the onset of T2DM and obesity. However, these genes explain
only a fraction of the cases, leaving the majority unaccounted for. The missing heritability question
implies that other factors are responsible for the onset and development of the disease. Given that
the developing fetus is susceptible to the maternal environment, a growing body of evidence
demonstrates that maternal metabolic characteristics as well as disruptions to the prenatal environment
may induce long-term genetic, phenotypic, and physiologic adaptations in the developing fetus,
which could have a permanent effect on its future health. This phenomenon is known as developmental
programming and is mediated through epigenetic modifications, which include modulation
of gene expressions that do not alter the original deoxyribonucleic (DNA) sequence. Epigenetic
modifications are capable of changing gene expression in metabolism-related genes and are accomplished
through DNA methylation, histone acetylation, and ribonucleic acid (RNA) mechanisms.
In this review, we discuss maternal metabolic factors, such as obesity, dyslipidemia, and
gestational diabetes (GDM) that lead to epigenetic changes in the offspring and predispose future
generations to metabolic abnormalities. We will also describe the association between maternal
lifestyle factors and exposure to toxins with epigenetic modulations in the offspring. Lastly, we
will provide a brief review of the possibility of using epigenetics as potential interventions and
therapeutic modalities to help in early diagnosis and prevention of metabolic disorders.
Publisher
Bentham Science Publishers Ltd.
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism
Cited by
2 articles.
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