Effects of Maternal High‐Fat Diet During Pregnancy and Lactation on Behaviour and Hypothalamic Orexin Neurons in Mice Offspring

BACKGROUND: Maternal obesity is a risk factor for neurodevelopmental disorders in the offspring. In recent years, it has been suggested that not only maternal obesity but also dietary intake during pregnancy and lactation may influence children's behaviour and neurodevelopment. In the present study, we aimed to evaluate the effects of maternal high-fat diet (HFD) exposure during pregnancy and lactation on offspring locomotion and orexin neuronal activity in the lateral hypothalamus (LH). METHODS: Dams were fed either an HFD or a control diet (CD) during pregnancy and lactation. After weaning, their offspring were fed a CD. Male and female offspring were evaluated for behaviour at age 5 weeks using the open field test (OFT) and elevated plus maze (EPM) test. To investigate age-related effects, the same male offspring were further evaluated at age 5, 13 and 25 weeks using the OFT. Immunohistochemical staining was performed at age 5-6 weeks to quantify orexin A-positive neurons in the LH. Double staining for orexin A and c-Fos was conducted in the brains collected at 1-1.5 h after the OFT. RESULTS: In male offspring at age 5-6 weeks, the HFD group exhibited a significantly higher total distance in both the OFT and EPM compared with the CD group. The number of orexin A-positive neurons in the LH was higher in the HFD group than that in the CD group. However, significant differences were not observed in females. In the longitudinal assessment of male offspring, the total distance in the OFT significantly increased in the HFD group at age 5 and 13 weeks but showed no significant difference at age 25 weeks. Furthermore, double staining for orexin A and c-Fos in 5- to 6-week-old male offspring revealed significantly higher co-localisation in the HFD group than in the CD group. CONCLUSIONS: Maternal HFD exposure during pregnancy and lactation increases locomotor and orexin neuronal activity in male offspring; however, these effects diminish with age. These results suggest that a short duration of maternal HFD exposure may enhance locomotor activity in male offspring, especially juveniles, via the alteration of orexin neuronal activity in the LH.