Does Obesity Have More to Do with the Brain Than We Initially Thought?

Obesity can seriously compromise a person’s physical and mental health. It is defined as “abnormal or excessive fat accumulation that may impair health” and is a known risk factor for heart disease, type 2 diabetes, and certain cancers— all of which are leading causes of preventable, premature death.

Rates of obesity have tripled since 1975, over 41% of adults and almost 20% of children in the U.S. are classed as obese. People are considered obese if they have an excess of body fat and a Body Mass Index (BMI) over 30.

BMI is a simple but rather controversial measurement, defined as a person’s weight in kilograms divided by the square of their height in meters (kg/m2).

Recently, researchers at Baylor College of Medicine suggested that obesity risk in humans may be determined by environmental and genetic factors during early development and argue that obesity should be considered a neurodevelopmental disease.

Study lead Dr. Robert A. Waterland, professor at Baylor College of Medicine, told ishonest:

“[…] genetic variation certainly contributes to individual differences in body weight, early environmental influences on the development of body weight regulatory mechanisms (developmental programming) may, in general, play a bigger role in determining individual propensity to obesity.”

What causes obesity

A number of things such as poor diet, lack of physical exercise, and a lack of “good” sleep, are known to increase the risk of obesity.

The type and amount of food eaten are also directly linked to obesity risk, consuming an excess of calories and burning very few will create a calorie surplus leading to weight gain. That said, the public health message to eat less and exercise more hasn’t stemmed the tide of obesity.

Once seen as a result of a lack of will and self-restraint, the biological nature of obesity has been shown to be much more complex. Indeed, prenatal and early life studies have linked undernutrition to obesity in rats.

The effect of nutrition during early development in human studies has shown famine during the first trimester of pregnancy resulted in higher obesity rates, but famine during the last trimester and the first months of life was linked with lower levels of obesity.

It is widely accepted that body weight is also influenced by genetics. The CDC reports over 50 different genes that have been associated with obesity. Genes determine the signals that are transmitted by hormones to the brain, where they direct the body to eat or move.

Large-scale human genome studies have found changes in genes linked to BMI are expressed in the developing brain.

Changing how the body reads DNA

Epigenetics studies the way genes work, allowing scientists to study how behavior and environment can alter how genes work. Epigenetic changes don’t change the sequence of the DNA, they change how the body reads the DNA sequence.

For this study, mice aged 2 to 4 months were monitored through pregnancy and their pups were studied through post-natal development.

Whole genome analysis and RNA sequencing were completed on neuron and glia cells and studied for epigenetic markers and gene expression. Specifically, the researchers used tissue from the arcuate nucleus of the hypothalamus of the brain, the area that controls hunger and satiety.

Interestingly, when comparing the epigenetic data with data from human genome studies the investigators found a strong correlation between regions of the human genome linked to BMI and the areas of epigenetic changes in mice, leading to the suggestion that adult obesity may be determined in part by epigenetic development in the arcuate nucleus.

Interventions to prevent obesity

“[E]vidence from the last several decades indicates that once an individual is obese, it is extremely difficult to achieve a ‘normal’ body weight. And, when obese adults do succeed in losing substantial weight, it is extremely difficult to maintain the weight loss in the long term. It is our hope that an improved understanding of the developmental neuroepigenetic mechanisms underlying the establishment of body weight regulation will enable effective approaches to prevent obesity.”— Dr. Robert A. Waterland

When asked if the work could lead to new nutritional recommendations for pregnancy, Dr. Waterland commented that the current research, which was conducted in mice, “does not provide a basis for making nutritional recommendations for humans. Although we don’t yet have the data, it is a reasonable guess that the postnatal epigenetic maturation we cataloged in this mouse study occurs during late fetal development in humans”.

“[…] such data would bolster existing recommendations that women try to achieve a healthy body weight prior to becoming pregnant, as maternal obesity during pregnancy not only raises the risk of pregnancy complications like preterm birth and gestational diabetes but also appears to promote lifelong positive energy balance in her developing child,” he added.

The study is not without limitations.

The nature of the ever-changing cell population during early development makes interpreting the data complicated, it is possible that changes in the cell population between the time points may affect the results.

The next steps

The next step for the research is to extend it into human studies.

“[…] an obvious next step is to determine when this BMI-associated epigenetic maturation occurs in humans. Because many neurodevelopmental processes occur earlier in humans than in mice, it is likely that this hypothalamic epigenetic maturation occurs during late fetal development in humans,” said Dr. Waterland.

“[A]n obvious next step would be to try to determine if maternal obesity during pregnancy somehow impairs these developmental changes, resulting in persistently impaired regulation of energy balance in her child.”— Dr. Robert A. Waterland

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