Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety-like behavior in nonhuman primate offspring

Abstract

Childhood obesity is associated with increased risk of behavioral/psychological disorders including depression, anxiety, poor learning, and attention deficient disorder. As the majority of women of child-bearing age are overweight or obese and consume a diet high in dietary fat, it is critical to examine the consequences of maternal overnutrition on the development of brain circuitry that regulates offspring behavior. Using a nonhuman primate model of diet-induced obesity, we found that maternal high-fat diet (HFD) consumption caused perturbations in the central serotonergic system of fetal offspring. In addition, female infants from HFD-fed mothers exhibited increased anxiety in response to threatening novel objects. These findings have important clinical implications as they demonstrate that exposure to maternal HFD consumption during gestation, independent of obesity, increases the risk of developing behavioral disorders such as anxiety.

Figure 1.

Maternal high-fat diet consumption causes perturbations in the serotonergic system of fetal offspring. a–c, HFD offspring displayed increased TPH2 mRNA in the rostral raphe (a; p = 0.03, n = 8), increased 5-HT1AR mRNA (b; p = 0.03, n = 6); and no difference in SERT mRNA (c; p = 0.60, n = 5) compared to CTR offspring. Aq, Aqueduct; 4N, trochlear nerve; MnR, median raphe nucleus. Scale bars, 1 mm.

Figure 2.

Maternal high-fat diet consumption increased anxiety-like behavior in female offspring. a, b, Female offspring from HFD-fed mothers display increased latency to touch Mr. Potato Head (a; p = 0.01) and the rubber snake (b; p = 0.04) compared to female CTR offspring. c, d, There was no difference in the latency to touch the hanging bird toy (c; p = 0.16) or the kiwi fruit (d; p = 0.32) between female HFD and CTR offspring. Male HFD and CTR offspring had a similar response to Mr. Potato Head (a; p = 0.41), the rubber snake (b; p = 0.75), the hanging bird toy (c; p = 0.66), and the kiwi fruit (d; p = 0.95). Data are presented such that each point represents an animal (●, male offspring; ×, female offspring. *p < 0.05 when comparing female CTR and HFD offspring. For the CTR group, n = 4 male and 4 female offspring; for the HFD group, n = 12 male and 11 female offspring.