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

Abstract

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-6 high /n-3 low 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-6 high /n-3 low 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-6 high /n-3 low diet. Our findings reveal that maternal consumption of PUFAs can have long-lasting effects on the offspring's pattern for consuming highly palatable foods.

Characterization of the fatty acid profile in the ventral midbrain of mice exposed to dietary imbalance between omega-6 and omega-3 fatty acids during specific life stages

“…The control and n -6 high / n -3 low diets [ 12 ] were manufactured by Clea Japan Inc. The control diet was based on the AIN-93G diet [ 24 ] and was formulated to contain the following components: 51.9486 g cornstarch, 1 g α-cornstarch, 10 g sucrose, 7 g soybean oil (Additional file 1 : Table S1), 1.4 mg tert-butylhydroquinone, 20 g milk casein, 0.3 g L-cystine, 5 g cellulose powder, 3.5 g AIN-93G mineral mix, 1 g AIN-93 vitamin mix, and 0.25 g choline bitartrate per 100 g complete diet.…”

“…The control diet was based on the AIN-93G diet [ 24 ] and was formulated to contain the following components: 51.9486 g cornstarch, 1 g α-cornstarch, 10 g sucrose, 7 g soybean oil (Additional file 1 : Table S1), 1.4 mg tert-butylhydroquinone, 20 g milk casein, 0.3 g L-cystine, 5 g cellulose powder, 3.5 g AIN-93G mineral mix, 1 g AIN-93 vitamin mix, and 0.25 g choline bitartrate per 100 g complete diet. The n -6 high / n -3 low diet was produced by replacing soybean oil in the control diet with high-linoleic safflower oil (Additional file 1 : Table S1), as previously reported [ 10 – 12 , 23 ]. Consequently, the n -6 high / n -3 low diet contained more LA (18:2 n -6) and less ALA (18:3 n -3) than the control diet (Table 1 ).…”

“…n -6 and n -3 PUFAs are generally competitive in various metabolic processes, and the n -6/ n -3 ratios of PUFAs that compose our bodies and our diets warrant particular attention [ 5 , 16 ]. Regarding recent nutritional trends leading to foods that are high in n -6 PUFAs and low in n -3 PUFAs [ 17 , 18 ], life-long exposure to a diet high in n -6 and low in n -3 PUFAs (an n -6 high / n -3 low diet) beginning from conception to adulthood increased the levels of ARA and n -6 DPA and decreased that of DHA in the offspring’s whole brain during the embryonic, early postnatal, and adult periods compared to the offspring’s whole brain exposed to a well-balanced control diet [ 11 , 12 ]. In parallel with such changes in the brain fatty acid profile, life-long exposure to the n -6 high / n -3 low diet resulted in increased sucrose intake in the offspring compared to the offspring exposed to the control diet [ 12 ].…”

“…Regarding recent nutritional trends leading to foods that are high in n -6 PUFAs and low in n -3 PUFAs [ 17 , 18 ], life-long exposure to a diet high in n -6 and low in n -3 PUFAs (an n -6 high / n -3 low diet) beginning from conception to adulthood increased the levels of ARA and n -6 DPA and decreased that of DHA in the offspring’s whole brain during the embryonic, early postnatal, and adult periods compared to the offspring’s whole brain exposed to a well-balanced control diet [ 11 , 12 ]. In parallel with such changes in the brain fatty acid profile, life-long exposure to the n -6 high / n -3 low diet resulted in increased sucrose intake in the offspring compared to the offspring exposed to the control diet [ 12 ]. As sucrose intake behavior is strongly mediated by the ventral midbrain dopamine system [ 19 ], these data indicate that increased and/or decreased levels of PUFAs in the adult brain might augment the dopamine system, which was also proposed by another study [ 20 ].…”

“…In addition to the well-accepted notion that n -6 and n -3 PUFAs that compose the adult brain control various behaviors [ 5 ], recent birth cohort studies have found that maternal dietary n -6 and n -3 PUFAs are relevant to offspring behaviors in childhood [ 21 , 22 ]. In animal studies, we also found that increased levels of ARA and n -6 DPA and decreased levels of DHA in the embryonic and early postnatal whole brain of the offspring exposed to the n -6 high / n -3 low diet [ 11 ] were completely recovered to control levels in the adult whole brain of the offspring exposed to diets adequate in ALA from the early postnatal period to adulthood [ 23 ]; nevertheless, maternal exposure to the n -6 high / n -3 low diet limited to the gestation period similarly led to increased sucrose intake in the offspring [ 12 ]. Thus, it is likely that offspring in utero exposed to the n -6 high / n -3 low diet show increased sucrose intake without significant changes in the fatty acid profile of the adult whole brain.…”