Published online Apr 15, 2021. doi: 10.4239/wjd.v12.i4.366
Peer-review started: January 16, 2021
First decision: January 24, 2021
Revised: January 30, 2021
Accepted: February 18, 2021
Article in press: February 18, 2021
Published online: April 15, 2021
According to the developmental origin of health and disease concept, the risk of many age-related diseases is not only determined by genetic and adult lifestyle factors but also by factors acting during early development. In particular, maternal obesity and neonatal accelerated growth predispose offspring to overweight and type 2 diabetes (T2D) in adulthood. This concept mainly relies on the developmental plasticity of adipose tissue and pancreatic β-cell programming in response to suboptimal milieu during the perinatal period. These changes result in unhealthy hypertrophic adipocytes with decreased capacity to store fat, low-grade inflammation and loss of insulin-producing pancreatic β-cells. Over the past years, many efforts have been made to understand how maternal obesity induces long-lasting adipose tissue and pancreatic β-cell dysfunction in offspring and what are the molecular basis of the transgenerational inheritance of T2D. In particular, rodent studies have shed light on the role of epigenetic mechanisms in linking maternal nutritional manipulations to the risk for T2D in adulthood. In this review, we discuss epigenetic adipocyte and β-cell remodeling during development in the progeny of obese mothers and the persistence of these marks as a basis of obesity and T2D predisposition.
Core Tip: According to the developmental origin of health and disease concept, maternal obesity and neonatal accelerated growth predispose offspring to metabolic diseases. White adipose tissue and pancreatic β-cells are key targets of developmental programming, although the underlying mechanisms remain elusive. Human and rodent studies have contributed to decipher the role of epigenetic mechanisms in the transgenerational inheritance of obesity and type 2 diabetes (T2D). In this review, we discuss the current understanding of the link between obesogenic maternal nutritional environment, developmental epigenetic adipocyte and β-cell remodeling and predisposition to obesity and T2D later in life.