Parental obesity-induced changes in developmental programming

Abstract

Many studies support the link between parental obesity and the predisposition to develop adult-onset metabolic syndromes that include obesity, high blood pressure, dyslipidemia, insulin resistance, and diabetes in the offspring. As the prevalence of obesity increases in persons of childbearing age, so does metabolic syndrome in their descendants. Understanding how parental obesity alters metabolic programs in the progeny, predisposing them to adult-onset metabolic syndrome, is key to breaking this cycle. This review explores the basis for altered metabolism of offspring exposed to overnutrition by focusing on critical developmental processes influenced by parental obesity. We draw from human and animal model studies, highlighting the adaptations in metabolism that occur during normal pregnancy that become maladaptive with obesity. We describe essential phases of development impacted by parental obesity that contribute to long-term alterations in metabolism in the offspring. These encompass gamete formation, placentation, adipogenesis, pancreas development, and development of brain appetite control circuits. Parental obesity alters the developmental programming of these organs in part by inducing epigenetic changes with long-term consequences on metabolism. While exposure to parental obesity during any of these phases is sufficient to alter long-term metabolism, offspring often experience multiple exposures throughout their development. These insults accumulate to increase further the susceptibility of the offspring to the obesogenic environments of modern society.

How can paternal obesity impair memory processes in offspring?

“…There is a growing awareness that parental obesity may lead to adverse long‐term health consequences for subsequent generations. Both epidemiological and animal studies have provided evidence suggesting that either maternal or paternal obesity independently increases the risk of obesity, metabolic disorders, and mental health impairments in offspring 3–5 . A recent meta‐analysis of observational human studies indicated that specifically paternal obesity, rather than overweight, was significantly associated with mental disorders in offspring, such as anxiety, attention‐deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) 5 .…”

“…Both epidemiological and animal studies have provided evidence suggesting that either maternal or paternal obesity independently increases the risk of obesity, metabolic disorders, and mental health impairments in offspring. [3][4][5] A recent meta-analysis of observational human studies indicated that specifically paternal obesity, rather than overweight, was significantly associated with mental disorders in offspring, such as anxiety, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). 5 However, establishing a casual link between parental obesity and neurocognitive development in offspring has been challenging in human studies, primarily due to the confounding effects of genetic factors and postnatal environment.…”

Perinatal Factors and its Association with Cardiometabolic Profile in Schoolchildren

“…Developmental origins of health and disease hypothesis propose a connection between the periconceptual, fetal, and early infant stages of life and the sustained development of metabolic disorders [1,2]. The risk of developing a disease at any point in one's life is shaped by the interplay between genetics and the cumulative impact of lifestyle and environmental exposures across the lifespan [3].…”