Overeating During Pregnancy Alters Feeding Behaviors in Children

Overweight and obese conditions have exploded in the industrialized world. These conditions are directly tied to increased morbidity and mortality from the associated pathologies of hypertension, type 2 diabetes, cardiovascular disease, and strokes. These conditions and their negative impacts on productivity, the costs of treating and caring for overweight and obese individuals, not to mention the added costs associated with handling all the extra weight (think fuel burn on airplanes as an example) is estimated to cost the United States alone nearly 1 trillion dollars ($1,000,000,000,000) per year

There are many places where the blame can be pointed, lack of exercise, sedentary lifestyles, consumption of too much sugar, and consumption of highly refined foods. And yes ALL of these are to blame. Evidence is accumulating every year that the causes of obesity are transgenerational, meaning that the lifestyle of over consumption is passed on from one generation to the next. The simple approach to this problem is that if Mom and Dad eat too much so too will their children since they will be fed meals with excessive calories. However, this is not the whole, nor the most important factor contributing to transgenerational obesity.

The primary control over the desire to consume food, and what type of foods are deemed palatable, is exerted by neural circuits in the brain. The primary centers in the brain involved in the control of appetite are the hypothalamic-pituitary axis and the brain stem. Theses brain regions play highly critical roles in the regulation of energy metabolism, nutrient partitioning, and the control of feeding behaviors.

The gastrointestinal tract is intimately connected to the actions of the brain in metabolic and appetite control, in a large part, through interactions with the hypothalamic-pituitary axis. These gut-brain interactions occur via the release of gut peptides that exert responses within the brain as well as through neuroendocrine and sensory inputs from the gut.

The hypothalamus is located below the thalamus and just above the brain stem and is composed of several domains (nuclei) that perform a variety of functions. The hypothalamus forms the ventral portion of the region of the brain called the diencephalon. The primary nuclei of the hypothalamus that are involved in feeding behaviors and satiety (the sensation of being full) include the arcuate nucleus of the hypothalamus (ARC, also abbreviated ARH), the dorsomedial hypothalamic nucleus (DMH or DMN), the ventromedial hypothalamic nucleus (VMH or VMN), and the lateral hypothalamic area (LHA). The ARC is involved in the control of feeding behavior as well as in the secretion of various pituitary releasing hormones. The DMH is involved in stimulating gastrointestinal activity. The VMH is involved in neural signals that elicit the sensations of satiety. The medial hypothalamic nuclei (VMH and to a lesser extent the DMH) are responsible for the sensations of satiety and lesions in these regions of the hypothalamus result in hyperphagia (excessive hunger) and obesity. The LHA is responsible for transmitting orexigenic signals (desire for food intake) and loss of this region results in starvation. Conversely, stimulation of the LHA results in increased food consumption and weight gain.

Overall appetite is a complex process that results from the integration of multiple signals at the hypothalamus. The hypothalamus receives neural signals, hormonal signals, such as leptin, cholecystokinin (CCK), and ghrelin, and nutrient signals such as glucose, free fatty acids, amino acids, and volatile (short-chain) fatty acids. These effects are processed by a specific sequence of neurotransmitters beginning within domains of the ARC that consist of orexigenic (appetite stimulation) neurons expressing neuropeptide Y (NPY) and Agouti-related peptide (AgRP) as well as domains that consist of anorexigenic (appetite suppressing) neurons expressing pro-opiomelanocortin, POMC (yielding the neurotransmitter, alpha-melanocyte stimulating hormone: α-MSH) and cocaine and amphetamine-regulated transcript (CART).

With respect to the LHA, evidence has shown that in response to acute and long-term changes in energy balance in adults, significant alterations in the expression of numerous genes occurs. In addition, the LHA has been shown to undergo physiological changes during pregnancy when the mother consumes excess calories, beyond that required to sustain fetal development and maternal health. When experiments are carried out in animals it has been shown that the offspring from overweight females have increased expression of orexigenic neuropeptides within the LHA.

A new report published in the journal, Molecular Metabolism, demonstrates that when the mother overeats there are dramatic changes taking place in the hypothalamus, in this report the LHA, that result in engrained overeating behaviors in offspring:

Maternal overnutrition is associated with altered synaptic input to lateral hypothalamic area

Although this study involved laboratory rodents, the results are directly applicable to humans since the brain regions, the neuropeptides, and the responses are identical in humans.

Maternal overnutrition was induced by allowing the female mice to consume a obesity-inducing diet prior to mating, during gestation, and throughout lactation.

Female mice in this study were given ad libitum (meaning whenever they wanted) access to either high fat diet (HFD) and standard chow or a taste matched low fat diet (LFD). The HFD was 60% calories from fat, the standard chow was 21% calories from fat, and the LFD was 16% calories from fat. The males with whom these test females were mated were fed standard chow only. This allowed for assessment of dietary composition of the mothers and the impacts on offspring.

When the offspring of the overnutrition females were examined as adults, all mice born from mothers who consumed the HFD showed a strong preference for the HFD over the LFD, and over standard chow. These phenomena were apparent in both male and female offspring.

With respect to effects within the hypothalamus it was already known that maternal overnutrition resulted in increased expression of orexigenic neuropeptides as well as increased neurogenesis and synaptic innervation within the LHA.

This study found that maternal overnutrition is associated with increased neuronal excitability in the LHA of offspring. This increased excitability is primarily associated with inhibitory neurons that release the neurotransmitter, gamma-aminobutyric acid (GABA). This leads to inhibition of anorexigenic neuropeptide release. The overall consequence is enhanced desire to consume food and reduced ability to suppress those increased feeding desires.

TAKE HOME: The results from this study add yet another "nail in the coffin" that is the result of the consumption of too many calories, especially from fat, while pregnant. The result being that the fetuses exposed to this type of environment in the uterus will grow up to have limited control of their desire to eat. Take this out with each successive generation and you have a clear picture of one of the most significant contributors to the current worldwide epidemic obesity.