Clinical and experimental studies suggest that prenatal and early postnatal exposure to maternal obesity can adversely affect behaviour and cognitive function in the offspring. Cerebral mitochondrial dysfunction and oxidative stress are possible mechanistic links. This study determined the impact of maternal diet-induced obesity during pregnancy and lactation on cerebral mitochondrial function in adult offspring.
Under the Animals (Scientific Procedures) Act 1986, female C57BL6/J mice were fed either a diet high in fat and sugar (HFHS, fat: 36% kcal, sugar: 29.5% kcal) or a standard chow diet (Control, fat: 11% kcal, sugar: 7% kcal) for 6 weeks prior to mating, during pregnancy and lactation. After birth, litter sizes were standardised to 6, and all offspring were weaned onto standard chow. At 14 weeks postnatal age, male (Control n=4; HFHS n=3) and female (Control n=4; HFHS n=4) offspring were euthanised and high-resolution respirometry employed to assess mitochondrial respiration in the hypothalamus, hippocampus and frontal cortex. Data were analysed using a two-way ANOVA.
In the hypothalamus, Complex I (CI)-linked respiration was 11% higher in HFHS offspring (p=0.049). Further, the respiratory reserve capacity of the electron transport chain (the difference between maximal oxidative phosphorylation (OXPHOS) and FCCP-uncoupled respiration) was 6% lower in HFHS offspring (p=0.049). In the hippocampus, there was a significant interaction (p=0.032) between maternal obesity and sex for the respiratory control ratio, which reflects the coupling efficiency of ADP-stimulated respiration, with 10% lower coupling seen in HFHS male offspring compared to control male offspring (P=0.040). In addition, an overall interaction was observed for OXPHOS supported by CI & Complex II (CII)-linked substrates (P=0.040). There was no effect of maternal obesity on mitochondrial respiratory function in the cortex.
Exposure to an obesogenic environment in early life can impair mitochondrial bioenergetics in different brain regions in a sex-specific manner with implications for cerebral function.