Location: Healthy Body Weight Research
2020 Annual Report
Objectives
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.
Approach
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.
Progress Report
The new project plan started in fiscal year 2020. Under Objective 1, studies were conducted 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 a potential underlying mechanism revealed that placental hypoxia and reduced blood flow may contribute to in utero growth restriction. Investigation of a 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 have been initiated addressing how maternal vegetable or probiotic supplementation alter placental structure and function to influence fetal growth. Results from all of these studies will help formulate optimal maternal, paternal postnatal diet and exercise conditions for prevention of offspring obesity.
Accomplishments
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 onset obesity and type 2 diabetes in offspring. However, whether maternal low-protein diet causes learning and memory deficits has not yet been determined. In collaborative mouse model studies, 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 a maternal high fat diet-induced fatty placenta and fetal weight reduction: Role of probiotic supplementation. Maternal (mother’s) obesity hinders fetal growth by restricting blood supply to the fetus. Probiotics play a beneficial role in reducing inflammation and by providing metabolic energy to host cells. Whether supplementing a maternal high fat diet with probiotic bacteria often found in yogurt helps to restore detrimental effects of a maternal high fat diet is not known. Researchers in Grand Forks, North Dakota, tested the association between fat content of the placenta and fetal growth at the mid- and late- gestational periods and showed that probiotic supplementing provided beneficial effects in reducing placental tissue fat content at the mid-gestational period. This knowledge contributes to understanding the optimal maternal diet composition prior to conception in animal and eventually in human populations so that offspring type 2 diabetes risk can be reduced.
3. Effects of calcium transporter protein deactivation on the regulation of body weight under exercised conditions. Adipose tissue energy metabolism is regulated in part by calcium levels in cells. It is not known whether lacking a calcium transporter protein in mice results in increased risk for development of obesity and type 2 diabetes mellitus. Using mice lacking calcium transporter protein, researchers in Grand Forks, North Dakota, demonstrated that calcium transport plays an important role in the regulation of body weight and adiposity, and that loss of calcium transporter protein promotes exercise-induced protection against high-fat diet-induced obesity and type II diabetes. This knowledge contributes to understanding the optimal maternal diet composition prior to conception in animal and eventually in human populations so that offspring type 2 diabetes risk can be reduced.
4. Placental tissue inflammation and nutrient transporter gene expression are regulated by paternal diet and exercise conditions. Several studies indicated that paternal obesity increases, while paternal exercise decreases, offspring obesity and type 2 diabetes risk; however, none had yet to determine whether a paternal high fat (HF) diet and exercise modify placental tissue weight and inflammation, fetal weight, and nutrient transport by changing sperm microRNA. Researchers in Grand Forks, North Dakota, showed that paternal HF diet decreases sperm’s epigenetic marker protein expression. Paternal exercise also modified sperm expression of microRNA (miRNA) a known regulator of gene expression. A paternal HF diet decreased placental and fetal weights in placenta of male fetuses while nutrient transporters and inflammatory factor (IL-1 beta and TNF-alpha) mRNA expression were altered only in placenta of female fetuses. This knowledge contributes to understanding of how a paternal HF diet and exercise influence placental and fetal weight, placental inflammation and nutrient transport in offspring in a sex-specific manner.
Review Publications
Larson, K.J., Alvine, T., Wu, D., Kalupahana, N., Moustaid-Mouss, N., Roemmich, J.N. 2020. Nutrients and immunometabolism: Role of macrophages. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa085.
Strahm, A., Bagne, A., Rued, H., Larson, K.J., Roemmich, J.N., Hilmert, C. 2020. Prenatal traumatic stress and offspring hair cortisol concentration: A nine year follow up to the Red River Flood Pregnancy Study. Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2019.104579.
Larson, K.J., Bundy, A.N., Roemmich, J.N. 2020. Paternal high fat diet and exercise regulate sperm miRNA and histone methylation to modify placental inflammation, nutrient transporter mRNA expression, and fetal weight in a sex-dependent manner. Journal of Nutritional Biochemistry. https://doi.org/10.1016/j.jnutbio.2020.108373.
