Maternal Over- and Malnutrition and Increased Risk for Addictive and Eating Disorders in the Offspring

Abstract

Evidence from human and animal studies has shown that maternal overnutrition and/or obesity are linked with neurobehavioral changes in the offspring. This fetal programming is characterized by adaptive responses to changes in the nutritional state during early life. In the past decade, an association has been made between overconsumption of highly-palatable food by the mother during fetal development and abnormal behaviors resembling addiction in the offspring. Maternal overnutrition can lead to alterations in the offspring's brain reward circuitry leading to hyperresponsiveness of this circuit following exposure to calorie-dense foods later in life. Given the accumulating evidence indicating that the central nervous system plays a pivotal role in regulating food intake, energy balance, and the motivation to seek food, a dysfunction in the reward circuitry may contribute to the addiction-like behaviors observed in the offspring. However, the underlying mechanisms leading to these alterations in the reward circuitry during fetal development and their relevance to the increased risk for the offspring to later develop addictive-like behaviors is still unclear. Here, we review the most relevant scientific reports about the impact of food overconsumption during fetal development and its effect on addictive-like behaviors of the offspring in the context of eating disorders and obesity.

Keywords: addiction; animals; eating disorders; high-fat diet; maternal overnutrition; obesity; offspring.

Figure 1

Animal models of maternal overnutrition (which includes high-fat, cafeteria—i.e., high-fat-high-sugar—diets, and which most closely mimic the obesogenic western diet in humans as a consequence of a tasty but unbalanced diet) during the periconceptional, gestational, and lactational periods have been key in our understanding of the non-genetic transfer of disease risk to the offspring. Exposure to these diets differs between studies, which results in dissimilarities (highlighted in bold) not only in maternal phenotype at the start of gestation, but also in changes in the central dopaminergic pathways in the offspring. These discrepancies of when maternal overnutrition exposure occurs can inform us about which periods of development are critical in inducing disorder susceptibility in the offspring and therefore, when to target interventions. D1/D1R: dopamine 1 receptor, D2/D2R: dopamine 2 receptor, DA: dopamine, DAT: dopamine transporter, DOPAC: 3,4-dihydroxyphenylacetic acid, dSTR: dorsal striatum, HYP: hypothalamus, MSN: medium spiny neuron, NAc: nucleus accumbens, PFC: prefrontal cortex, SN: substantia nigra, TH: tyrosine hydroxylase, VTA: ventral tegmental area, ↑: increase in, ↓: decrease in.

Figure 2

Summary of the possible mechanisms (in black) underpinning the negative effects (in blue) of maternal overnutrition on the offspring. The maternal overnutrition model is designed to test the impact of maternal (F0 generation) challenge with calorie dense foods on subsequent generations (F1, F2, F3) of male and female offspring consuming a standard chow. This schematic illustrates how such effects turn into a deleterious cycle as they are transmitted from one generation to the next. Note that peri-pregnancy overnutrition is necessary for the gestating female (F0 generation) but that the effects can be perpetuated in a transgenerational manner, even if the next-generation mothers (F1 which is the immediate offspring, second-generation (F2) offspring via the maternal or paternal lineage—i.e., male F1 offspring from over-nourished mothers are mated with naïve females to generate F2 offspring) eat a healthy diet during pregnancy. The epigenetic and other mechanisms leading to negative effects in the offspring can indeed also be transmitted by males (i.e., future fathers) to the next generation. F3, third generation offspring. ↑: increase in.