Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring

Abstract

Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed.

Models of Intrauterine growth restriction and fetal programming in rabbits

“…High dietary intake of fats and sugar can lead to obesity and babies from obese mothers have increased risks of neonatal complications, IUGR and the development of late‐onset diseases, including Type‐2 diabetes, cardiovascular disease, and obesity in adulthood (Frias & Grove, ; Glastras, Chen, Pollock, & Saad, ; Marchi, Berg, Dencker, Olander, & Begley, ; Tenenbaum‐Gavish & Hod, ). There is also evidence from small and large animal models that maternal consumption of an obesogenic diet affects prenatal development and programs changes in many physiological systems of the offspring, including the metabolic, cardiovascular, and reproductive (Armitage, Taylor, & Poston, ; Gonzalez‐Bulnes & Chavatte‐Palmer, ; Metges, ; Sferruzzi‐Perri & Camm, ; Williams et al, ).…”

Maternal obesity and offspring risk of chronic kidney disease

“…have previously reviewed multiple pathways of epigenetic changes and maternal‐foetal interaction as a consequence of maternal obesity that resulted in increased oxidative stress and mitochondrial dysfunction even during the oocyte developmental phase. In addition, maternal obesity during pregnancy can lead to placental oxidative stress, inflammation and vasculopathy that can potentially disrupt the blood‐placental barrier, leading to foetal exposure to otherwise restricted maternal factors, including excess nutrients, metabolic hormones and cytokines . Given the increased availability of glucose and lipid in obese individuals that, during pregnancy are prioritized for foetal usage, the foetus tends to undergo over‐nutrition‐related metabolic programming at early developmental periods.…”

“…In addition, maternal obesity during pregnancy can lead to placental oxidative stress, inflammation and vasculopathy that can potentially disrupt the blood-placental barrier, leading to foetal exposure to otherwise restricted maternal factors, including excess nutrients, metabolic hormones and cytokines. 19 Given the increased availability of glucose and lipid in obese individuals that, during pregnancy are prioritized for foetal usage, the foetus tends to undergo over-nutrition-related metabolic programming at early developmental periods. Through its effect on hypothalamic-appetite regulation, epigenetic changes may confer additional risks to appetite dysregulation and metabolic disorders later in life.…”

Diet‐induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity

“…Such studies have revealed that offspring of obese mothers exhibit elevated body fat, leptin cord blood, and cytokine levels (Catalano, Presley, Minium, & Hauguel‐de Mouzon, ), together with increased insulin, cholesterol, and blood pressure (Gaillard, ). The effects of maternal obesity persist into adulthood, increasing the risk for cancer, metabolic disorders (Glastras, Chen, Pollock, & Saad, ), impaired cognitive and executive functions, and neuropsychiatric problems (Mina et al, ; Pugh et al, ). The effects of high‐fat diet (HFD) and obesity in mice are similar to those in humans (Keleher et al, ).…”