Location: Healthy Body Weight Research2021 Annual Report
Objective 1: Demonstrate effects of parental diet and exercise on placental epigenetic programming that affects offspring obesity and type 2 diabetes mellitus. Objective 2: Determine the effects of maternal dietary patterns on placental tissue epigenetic programming and central dopaminergic control of offspring eating behavior. Objective 3: Define intervention strategies to reverse placental programming induced by parental high-fat diet.
The maternal and paternal consumption of excess food energy leading to parental obesity contributes to the subsequent development of offspring obesity. This phenomenon, in part, involves the epigenetic transmission of obesity risk across generations. The overarching hypothesis of this proposal is that a parental high fat diet and sedentary conditions regulate offspring obesity risk via modifying early epigenetic programming of placental tissue. We propose to study how these placental changes result in adipose and skeletal tissues energy metabolism and eating behavior alterations in the offspring. The primary focus of this project will be on placental tissue epigenetic gene expression influencing placental structural alterations and inflammation resulting in maternal nutrient transport dysfunction. Both animal and human studies show that maternal and paternal diets and obesity adversely affect fetal growth by altering placental structure and function, resulting in adverse birth outcomes and offspring obesity. Our preliminary data demonstrate that placental inflammation and nutrient transporter gene expressions are influenced by parental diet and exercise. Our new research project is an extension of our current and previous projects in which we demonstrated that maternal low protein and high fat diets increase placental tissue scarring, resulting in neovascularization and inflammation that increase offspring obesity and type 2 diabetes mellitus (T2DM) risks. There is little research on how maternal and paternal diets and exercise influence offspring obesity and T2DM risks via epigenetic-induced alterations in placental tissue function. Research results from this project will advance the field of Nutritional Programming in relation to prevention of offspring obesity.
The second year of new project plan started in Fiscal Year(FY) 21. Under Objective 1, studies continued to determine the effects of parental high fat diet on placental epigenetic and structural alterations that are associated with offspring obesity and peripheral metabolic tissue dysfunction. Consumption of maternal and paternal high fat diet induced placental lipid accumulation, inflammation, and decreased nutrient transporter gene expression to inhibit fetal growth. Investigation of potential underlying mechanism revealed that placental hypoxia and reduced blood flow may contribute to in utero growth restriction. Investigation of paternal high fat diet demonstrated that placental growth restriction may be caused by epigenetic alterations in the sperm microRNA. For Objective 2, studies addressing the effects of maternal high fat diet on offspring central dopaminergic physiology and eating behavior have been initiated. For Objective 3, studies addressing how maternal vegetable or probiotic supplementation alter placental structure and function to influence fetal growth have been initiated. Results from all these studies will help formulate optimal maternal, paternal postnatal diet and exercise conditions for prevention of offspring obesity.
1. A maternal diet influences expression of brain function markers in offspring. Maternal malnutrition is a major cause of low offspring birth weight and adult-on set obesity and type 2 diabetes in offspring. However, whether a maternal low-protein diet causes learning and memory deficits has not yet been determined. In a collaborative mouse model study, ARS researchers in Grand Forks, North Dakota, demonstrated that a maternal low-protein diet decreases a brain growth factor called brain-derived neurotrophic factor. This factor is important for learning and memory. This study contributed to increasing our knowledge toward how maternal malnutrition can have harmful effects on offspring brain function. This knowledge contributes to understanding the optimal maternal diet composition prior to conception in animal and eventually in human populations so that offspring brain dysfunction can be reduced.
2. Effects of calcium transporter protein deactivation on regulation of placental and fetal body weight. Maternal high fat (HF) diets affect placental and fetal growth and development differentially when this condition is also accompanied with lower levels of calcium in the placental cells. ARS researchers in Grand Forks, North Dakota, tested the effects of reduced placental cell calcium levels on maternal HF-induced placental dysfunction and showed that placental length, width, and weight as well as fetal weight were decreased in the mice with lowered calcium levels during pregnancy. Researchers in Grand Forks, North Dakota, also showed that this results in decreased two growth factors including placental and vascular endothelial growth factors. This knowledge contributes to understanding the optimal maternal diet and tissue calcium levels necessary for normal fetal growth.