Offspring of Mice Fed Imbalanced Diets Shown to Be Neurologically ‘Programmed’ for Obesity

Summary: Prenatal diet could increase the risk of unhealthy eating and obesity in the offspring, a new study reports. Pregnant mice fed high omega-6 and low omega-3 diets were more likely to have offspring that were more inclined to consume hyper-caloric foods, increasing their risk of obesity.

Source: Hiroshima University

Pregnant mice fed a diet high in omega-6 fats and low in omega-3 fats produce offspring that go on to exhibit “hedonic”–pleasurable but excessive–levels of consumption of hyper-caloric diets, according to researchers at Hiroshima University.

Omega-6 fats are found in grapeseed oil, corn oil and sesame oil, and are a staple of several salad dressings in world cuisine. Omega-3 fats are found in fish, perilla oil, and linseed oil. A diet balanced with these fats is considered essential for healthy brain growth.

The researchers also found that the offspring exhibit increased in utero growth of dopamine-producing neurons in the midbrain–the neurological reward system. They believe that exposure to this high omega-6/low omega-3 diet increases growth in these neurons in the fetus’s brain during a specific period during pregnancy, driving dopamine release in the offspring’s brain, and thus primes the offspring for hedonic consumption of sugar- or fat-rich diets over the course of their life.

The findings were published in the peer-reviewed journal Communications Biology, on August 28.

Meanwhile, mice whose mothers had not consumed the imbalanced omega-6/omega-3 diet did not exhibit as much overeating behavior, even when tempted by the presence of such food.

Since the 1960s, the Western diet has experienced a significant uptick in the presence of polyunsaturated omega-6 fats, and in ratios to polyunsaturated omega-3 fats that historically humans had never experienced before.

The ratio between these two types of fats is important because biochemically they compete with each other for incorporation into cell membranes, and an omega-6/omega-3 imbalance in the membranes of red blood cells is correlated with weight gain. An earlier study on mice had found that consumption of an imbalanced omega-6/omega-3 diet by the pregnant mother replicates this imbalance in the offspring’s brain and even impairs brain development.

The Hiroshima researchers also found that a dopamine-inhibiting drug eliminates the hedonic consumption of the offspring, further supporting the notion that the dopamine signaling plays a critical role in driving this behavior.

This shows dopamine neurons
The magenta staining shows brain cells that release dopamine. The green staining shows newly generated cells. The blue staining shows all cells. Image is credited to Nobuyuki Sakayori, Hiroshima University.

“This suggests that adult mice gorging themselves on hyper-caloric diets were in effect neurologically programmed to do so by their mother’s own consumption patterns,” said Nobuyuki Sakayori, paper author and assistant professor from the Graduate School of Biomedical and Health Sciences at Hiroshima University.

The scientists were keen to stress that the ratio of omega-6 to omega-3 fat in the mouse diet is much higher than that experienced by most humans, and that their work lays the foundation for further, epidemiological studies on humans to see if the pattern holds for us.

But if it does, this could provide a new strategy for preventing obesity in children by managing the type of fats that pregnant mothers consume, akin to how mothers today generally avoid consumption of alcohol.

“This could work much better than existing anti-obesity campaigns or food taxes,” Sakayori continued, “because instead of fighting against the brain’s reward system, such a strategy focuses right from the start on the development of that system.”

About this obesity research article

Hiroshima University
Norifumi Miyokawa – Hiroshima University
Image Source:
The image is credited to Nobuyuki Sakayori, Hiroshima University.

Original Research: Open access
“Maternal dietary imbalance between omega-6 and omega-3 fatty acids triggers the offspring’s overeating in mice” by Nobuyuki Sakayori, Masanori Katakura, Kei Hamazaki, Oki Higuchi, Kazuki Fujii, Ryoji Fukabori, Yoshio Iguchi, Susumu Setogawa, Keizo Takao, Teruo Miyazawa, Makoto Arita & Kazuto Kobayashi. Communications Biology.


Maternal dietary imbalance between omega-6 and omega-3 fatty acids triggers the offspring’s overeating in mice

The increasing prevalence of obesity and its effects on our society warrant intensifying basic animal research for understanding why habitual intake of highly palatable foods has increased due to recent global environmental changes. Here, we report that pregnant mice that consume a diet high in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and low in omega-3 (n-3) PUFAs (an n-6high/n-3low diet), whose n-6/n-3 ratio is approximately 120, induces hedonic consumption in the offspring by upregulating the midbrain dopaminergic system. We found that exposure to the n-6high/n-3low diet specifically increases the consumption of palatable foods via increased mesolimbic dopamine release. In addition, neurodevelopmental analyses revealed that this induced hedonic consumption is programmed during embryogenesis, as dopaminergic neurogenesis is increased during in utero access to the n-6high/n-3low diet. Our findings reveal that maternal consumption of PUFAs can have long-lasting effects on the offspring’s pattern for consuming highly palatable foods.

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