Unbalanced PUFA ratio deregulate dopamine in utero: and the offspring get “hedonic” on food

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. 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. 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.

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. Moreover, they are needed for a plethora of bioactive molecules involved in hormonal, inflammatory and immune functions, like prostaglandins, leukotrienes, resolvins and epoxylins. Some polyunsaturated fatty acids and their oxygenated derivatives are also ligands for cellular receptors that regulate intermediate metabolism (e.g. PPAR-alpha, PPAR-gamma, HNF-4, etc.).

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. 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 means that the unbalanced ratio of omega acids may affect the dopaminergic network even in utero.

Nobuyuki Sakayori, Study Author and Assistant Professor, Graduate School of Biomedical and Health Sciences, Hiroshima University, commented on the implications: “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. This could work much better than existing anti-obesity campaigns or food taxes, because instead of fighting against the brain’s reward system, such a strategy focuses right from the start on the development of that system.”

The findings were published on August 28 in the journal Communications Biology.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Sakayori N et al. Commun Biol 2020 Aug 28; 3(1):473.

Lo Van A, Sakayori N et al. Mol Neurobiol. 2019; 56(2):986. 

Sakayori N et al. Stem Cells. 2016 Feb; 34(2):470-82. 

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Informazioni su Dott. Gianfrancesco Cormaci 2450 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it
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