Epigenetic and developmental influences on the risk of obesity, diabetes, and metabolic syndrome

Abstract

Metabolic syndrome is a growing cause of morbidity and mortality worldwide. Metabolic syndrome is characterized by the presence of a variety of metabolic disturbances including obesity, hyperlipidemia, hypertension, and elevated fasting blood sugar. Although the risk for metabolic syndrome has largely been attributed to adult lifestyle factors such as poor nutrition, lack of exercise, and smoking, there is now strong evidence suggesting that predisposition to the development of metabolic syndrome begins in utero. First posited by Hales and Barker in 1992, the “thrifty phenotype” hypothesis proposes that susceptibility to adult chronic diseases can occur in response to exposures in the prenatal and perinatal periods. This hypothesis has been continually supported by epidemiologic studies and studies involving animal models. In this review, we describe the structural, metabolic and epigenetic changes that occur in response to adverse intrauterine environments including prenatal and postnatal diet, maternal obesity, and pregnancy complications. Given the increasing prevalence of metabolic syndrome in both the developed and developing worlds, a greater understanding and appreciation for the role of the intrauterine environment in adult chronic disease etiology is imperative.

Exposure of bovine oocytes and embryos to elevated non-esterified fatty acid concentrations: integration of epigenetic and transcriptomic signatures in resultant blastocysts

“…Some metabolism- or immune response-related genes are also associated with obesity and insulin resistance [41, 47–50]. Alterations in these pathways may further affect the offspring since maternal metabolic disorders have been shown to increase the risk of developing metabolic disorders in the offspring [51]. …”

Metabolism disrupting chemicals and metabolic disorders

“…Alterations of their levels during development by EDCs leads to tissues with abnormal gene expression, numbers of cells, location of cells, imbalance between cell types, as well as altered organ structure and hormonal signaling that lead to increased susceptibility to disease/dysfunctions across the life course [282, 285]. Adverse effects may be most pronounced in the developing organism and occur at concentrations of the chemical that are far below levels that would be considered harmful in the adult [286, 287]. Some of the reasons for this increased sensitivity include the fact that the protective mechanisms that are available to the adult, such as DNA repair mechanisms, a competent immune system, detoxifying enzymes, liver metabolism, and the blood/brain barrier are not fully functional in the fetus or newborn.…”

Nutrient regulation of gene expression by O-GlcNAcylation of chromatin

“…Many studies have highlighted the impact of nutrients or diabetes during pregnancy affecting offspring. Some of these effects are still detectable at the F3 and therefore transgenerational [44–48]. In the light that O-GlcNAcylation is deregulated under diabetes and obesity and considering its crucial role as a nutrient sensor and modulator of epigenetics, O-GlcNAcylation, as an epigenetic mark, could be one of the molecular mechanisms of nutrient- and stress-dependent non-DNA sequenced encoded inheritance phenotypes.…”