Maternal high fat diets: impacts on offspring obesity and epigenetic hypothalamic programming

Abstract

Maternal high-fat diet (HFD) during pregnancy is associated with rapid weight gain and fetal fat mass increase at an early stage. Also, HFD during pregnancy can cause the activation of proinflammatory cytokines. Maternal insulin resistance and inflammation lead to increased adipose tissue lipolysis, and also increased free fatty acid (FFA) intake during pregnancy (˃35% of energy from fat) cause a significant increase in FFA levels in the fetus. However, both maternal insulin resistance and HFD have detrimental effects on adiposity in early life. As a result of these metabolic alterations, excess fetal lipid exposure may affect fetal growth and development. On the other hand, increase in blood lipids and inflammation can adversely affect the development of the liver, adipose tissue, brain, skeletal muscle, and pancreas in the fetus, increasing the risk for metabolic disorders. In addition, maternal HFD is associated with changes in the hypothalamic regulation of body weight and energy homeostasis by altering the expression of the leptin receptor, POMC, and neuropeptide Y in the offspring, as well as altering methylation and gene expression of dopamine and opioid-related genes which cause changes in eating behavior. All these maternal metabolic and epigenetic changes may contribute to the childhood obesity epidemic through fetal metabolic programming. Dietary interventions, such as limiting dietary fat intake <35% with appropriate fatty acid intake during the gestation period are the most effective type of intervention to improve the maternal metabolic environment during pregnancy. Appropriate nutritional intake during pregnancy should be the principal goal in reducing the risks of obesity and metabolic disorders.

Dietary nutrients during gestation cause obesity and related metabolic changes by altering DNA methylation in the offspring

“…Recent animal and human studies show that a maternal high-fat diet (HFD) has an effect on the general health of the offspring including the development of obesity, diabetes mellitus, and cardiovascular diseases ( 40 – 43 ). Some of these phenotypic differences caused by a maternal HFD have been associated with epigenetic changes through several pathways ( 44 ).…”

Identifying of immune‐associated genes for assessing the obesity‐associated risk to the offspring in maternal obesity: A bioinformatics and machine learning

“…5 Changes in the development of the hypothalamus, a regulatory center for energy homeostasis and metabolic balance, are increasingly recognized as critical determinants of the offspring risk of metabolic disorders; however, the underlying mechanisms are only beginning to be understood. 7 Here, through…”

“… 5 Changes in the development of the hypothalamus, a regulatory center for energy homeostasis and metabolic balance, are increasingly recognized as critical determinants of the offspring risk of metabolic disorders; however, the underlying mechanisms are only beginning to be understood. 7 Here, through integrated bioinformatics analyses and machine learning methods, we identified two pivotal immune‐associated candidate genes ( Sytl4 and Kcnc2 ) and constructed a nomogram for diagnosing the obesity‐associated risk in the offspring of mothers with obesity.…”

“…The arcuate (Arc) nucleus of the hypothalamus comprises anorexigenic neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons and anorexigenic proopiomelanocortin (POMC) neurons, which subtly regulate the energy balance. 7 Recent evidence suggests that although neurons are fundamental to the physical functions of the hypothalamus, their proper function and systemic metabolic regulation largely rely on the surrounding non-neuronal cells, such as glia, epithelial cells, pericytes, and endothelia. 8 Aberrant nutritional elements, including fatty acids and glucose, transported into the hypothalamus primarily through the permeable blood-brain barrier (BBB), can induce glial activation and metaflammation within University, Grant/Award Number: KD2022KYCXTD005 Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro.…”

Close Adherence to a Mediterranean Diet during Pregnancy Decreases Childhood Overweight/Obesity: A Prospective Study

“…These factors are believed to reduce susceptibility to childhood weight gain by positively influencing fetal glucose metabolism and fetal metabolic function [ 46 , 47 ] while also supporting a favorable neonatal microbiome [ 48 ]. Other studies indicate that maternal deficiency in micronutrients such as vitamin D [ 49 ], folate [ 50 ], and ω-3 polyunsaturated fatty acids [ 51 ] during pregnancy, which is extremely prevalent, has the potential to indirectly impact offspring metabolic programming through epigenetic changes and to ultimately contribute to childhood obesity [ 35 ]. Conversely, maternal high-fat (especially saturated fat) diets also result in increased offspring adiposity by modifying DNA methylation and the gene expression of fetal hypothalamic appetite-related neurons and central reward system molecules, thus leading to alterations in appetite and energy metabolism in offspring [ 51 ].…”