Parental high-fat diets leave lasting marks on offspring brain development

A recent study published in Translational Psychiatry suggests that a parent’s consumption of foods high in fat and sugar before and during pregnancy can leave lasting physical marks on the developing brains of their offspring. Using a mouse model, scientists observed that early exposure to these diets alters the size of specific brain regions from infancy through adulthood, even if the offspring transition to a healthy diet early in life. The findings indicate that early nutritional environments might play a role in shaping long-term brain health and the risk for certain neurodevelopmental conditions.

Diet and metabolic health prior to birth are known to influence how the brain grows and functions. For example, a 2022 review article published in Frontiers in Neuroscience outlined the biological ways a maternal high-fat diet can influence this process. The review detailed that diets heavy in fat can trigger an inflammatory response in the body, alter the balance of gut bacteria, and change how certain genes operate in the developing fetus. These biological shifts in animals correspond to behavioral changes that resemble symptoms of human neurodevelopmental disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD).

Evaluating exactly when and how these physical brain changes occur has proven difficult in humans, as controlling and tracking dietary habits over many years is notoriously complex. To bypass these limitations, a research team led by Brian J. Nieman and Mark R. Palmert from The Hospital for Sick Children and the University of Toronto utilized a mouse model.

The researchers designed their experiment to map the precise timeline of brain structure development, looking to see if abnormalities emerge during gestation, puberty, or adulthood. Tracking this timeline provides insight into whether there might be specific developmental windows where interventions could prevent or repair diet-related brain alterations.

The experiment relied on 104 mouse offspring, split fairly evenly between males and females. The parents of these mice were randomly assigned to one of three diets starting in adolescence. One group ate a standard, healthy control diet. A second group ate a Western-style diet, which consisted of roughly 42 percent calories from fat and 34 percent simple sugar by weight.

A third group of parent mice ate a high-fat diet, which contained 60 percent calories from fat but a low amount of simple sugar. The parent mice ate these diets for eight weeks prior to breeding. The female mice continued their assigned diets through pregnancy and the three-week nursing period. Once the offspring reached three weeks of age and stopped nursing, the researchers transitioned all of them, regardless of their parents’ original group, onto the healthy control diet.

To observe how the brains changed over time, the scientists scanned the offspring using magnetic resonance imaging, or MRI, a technology that uses strong magnets to take detailed pictures of internal organs. They performed these brain scans at eight specific ages, starting three days after birth and ending at 150 days, which represents adulthood in mice. Across all time points, the team collected and analyzed 805 distinct brain images.

The researchers measured the volume of 182 separate brain structures within each scan. They then calculated the relative volume of each structure by comparing it to the total size of the animal’s whole brain, which helped them account for overall body and brain size differences. The statistical models also controlled for the age and sex of the mice.

The physiological results showed that parent mice on the Western and high-fat diets gained notably more weight than those on the control diet. For instance, the female mice on the Western diet gained an average of 5.9 grams, compared to 4.0 grams for the control group, representing a 48.5 percent relative increase in weight gain.

The offspring of the high-fat and Western diet groups were also born heavier. Males in these experimental groups weighed 14 percent more than control males at the time of weaning. However, once the offspring switched to the control diet, this weight difference vanished within a single week.

Despite normalizing their body weight, the offspring exposed to the Western and high-fat diets exhibited altered brain development trajectories. The researchers identified several distinct patterns of structural change. Some brain regions, such as the cerebral peduncle, a stem-like structure connecting different parts of the brain, were 2.7 to 2.9 percent smaller in relative volume in the diet-exposed groups at 14 days of age. This specific size difference faded slowly as the animals transitioned into adulthood.

Other brain regions showed early differences that lasted for the animal’s entire life. The relative volume of the cingulate cortex, a region involved in emotion and decision-making, was 1.2 to 2.0 percent larger in the diet-exposed newborn mice compared to the control group. By adulthood, this brain region remained 3.0 percent larger than the same region in the control mice.

A third pattern emerged where structural differences only appeared later in life, well after the mice had started eating a healthy diet. For example, the CA3 region of the hippocampus, which is critical for memory, showed no size differences at birth. By adulthood, the relative volume of this structure was 2.2 percent smaller in the Western diet group and 2.5 percent smaller in the high-fat diet group compared to the control animals.

Across the entire brain, the researchers noted a broader neuroanatomical trend related to early diet exposure. Cortical regions located on the brain’s outer layer tended to increase in relative volume over time. Deeper subcortical regions tended to decrease in volume over the lifespan of the animal.

Animal models provide a controlled environment to study biology, but humans experience vastly more varied diets and lifestyle factors. The observed percentage changes in a mouse’s brain volume do not act as a direct one-to-one map for a human child’s brain development. These findings do not imply that a parent’s diet permanently dictates a child’s brain health.

The observed differences in brain volume were relatively small, often ranging between one and three percent. It is not fully understood how these minor structural changes translate to actual behavioral or cognitive differences in the animals. The study relied on structural imaging, which measures the size and shape of brain regions, but this technique does not reveal how the cells within those regions are communicating or functioning.

Future investigations could test whether specific lifestyle adjustments, such as exercise or specialized nutritional supplements, might reverse or prevent these neurological changes. Researchers also plan to examine whether differences in maternal care, such as nursing and nesting behaviors, might indirectly contribute to some of the observed brain changes. Testing these variables alongside genetic predispositions could clarify how early life environments combine to influence the developing brain.

The study, “Parental high-fat/high-sugar diets and their lasting impact on brain development in offspring: a longitudinal mouse MRI study,” was authored by Gail Lee, Karina Wilk, Cheryl Chong, Jonas Yeung, Anne L. Wheeler, Jane A. Foster, Tie-yuan Zhang, Jason P. Lerch, Brian J. Nieman, and Mark R. Palmert.

The review article, “The impact of maternal high-fat diet on offspring neurodevelopment,” was authored by Gintare Urbonaite, Agne Knyzeliene, Fanny Sophia Bunn, Adomas Smalskys, and Urte Neniskyte.

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