Table 1.
Overview of preclinical studies investigating mechanisms of maternal-diet-induced obesity on the offspring brain and behaviour.
| Species (Strain) | Maternal Diet | Intervention Period, Length | Offspring Behavioural Outcomes | Offspring Brain Outcomes | Author, Year |
|---|---|---|---|---|---|
| Mouse (CD-1) | HFD (60% kcal fat) vs. CD (10% kcal fat) | Prenatal + postnatal, 12 weeks (including 6 weeks pre-gestation) | ↑ anxiety OFT PND21 and PND112; ↑ passive stress coping FST PND21 and PND112; ↓ social interaction PND56 | ↓ brain creatine and brain glutamate PND21; ↑ PFC ZIF-268 mRNA PND21; ↓ PFC SYP mRNA PND112 | Radford-Smith et al., 2022 [12] |
| Rat (Sprague Dawley) | HFD (60% kcal sat. fat) vs. trans fat (60% kcal trans-fat) vs. CD (10% kcal fat) | Prenatal + postnatal, 10 weeks (including 4 weeks pre-gestation) | ↑ anxiety EPM (males only), ↑ memory performance MWM in adulthood (3 months age) | ↑ hippocampal microglial activation (CD11b, TLR4) at PND1, ↑ IL-1B protein at PND20, ↑ hippocampal microglial activation and reactivity in adulthood (3 months age) | Bilbo and Tsang, 2010 [10] |
| Japanese macaques | HFD (32% kcal fat) vs. CD (13% kcal fat) | Up to 4 years (including prenatally) | ↑ anxiety female juvenile offspring (PND130) | ↑ TPH2, 5-HT1AR in dorsal raphe in foetuses; | Sullivan et al., 2010 [11] |
| Rat (Wistar) | HFD (40% kcal fat) vs. CD (12% kcal fat) | Gestation at lactation (until PND21) | ↓ anxiety in OFT, ↑ social interaction in HFD adult offspring experiencing maternal separation in early life compared to CD adult offspring | Prevents neurobiological effects (↓ BDNF, 5-HT1AR, CRH) of maternal separation stress in juvenile offspring (PND11) and anxiety-induced cFOS and corticosterone in adulthood (8 months). | Rincel et al., 2016 [13] |
| Mouse (C57Bl/6) | HFD (45% kcal fat) vs. CD (10% kcal fat) | 6 weeks (including gestation) | Pups exposed to HFD in utero altered maternal care behaviour (reduced time spent on nest) independent of maternal diet (cross-fostering experiment) | - | Baptissart et al., 2018 [14] |
| Rat (Long Evans) | HFD (60% kcal fat) vs. chow diet (13.5% kcal fat) | ~6 weeks (including 3 weeks pre-gestation) | Pup isolation test: HFD pups vocalised less at PND7, more at PND13 | ↑ CRH, ↓ NR3C1 in paraventricular nucleus at PND7, ↑ GAD1, ↓ NR3C1 in ventral hippocampus at PND13 | Abuaish et al., 2018 [15] |
| Mouse (C57Bl/6) | HFD (60% kcal fat) vs. chow diet (13.4% kcal fat) | Prenatal + postnatal, 14 weeks (including 8 weeks pre-gestation) | ↓ social interaction (3-chamber social interaction test), ↑ anxiety (OFT and marble burying) 7–12 week offspring | ↓ hypothalamic oxytocin in HFD offspring; ↓ social interaction-induced dopaminergic activity in ventral tegmental area | Buffington et al., 2016 [16] |
| Mouse (C57Bl/6) | HFD (45% kcal fat) vs. CD (10% kcal fat) | Variable pre-gestation until significant weight gain occurred | - | ↓ neuropeptide Y innervation of paraventricular nucleus in foetal offspring | Sanders et al., 2014 [17] |
| Mouse (C57Bl/6) | Chronic mild stress + Western diet (40% kcal fat) vs. no stress CD (10% kcal fat) | Prenatal + postnatal, 11 weeks (including 5 weeks pre-gestation) | - | ↑ hippocampal microglial activation (↑ CD11b+ cells, ↑ AIF1, TLR9 mRNA and protein); ↓ neuronal cell density (NeuN+ cells) in hippocampus | Cohen et al., 2016 [18] |
| Japanese macaques | HFD (36.6% kcal fat) vs. CD (14.7% kcal fat) | Mothers had been consuming HFD for 1.2–8.5 years at birth of offspring | ↑ anxiety and stereotypic behaviours in offspring (11 months age) | ↓ TPH2 mRNA in dorsal raphe; ↓ serotonin immunoreactivity prefrontal cortex (13 months age) | Thompson et al., 2017 [19] |
| Mouse (C57Bl/6) | HFD (60% kcal fat) vs. CD (10% kcal fat) vs. weight loss (HFD → CD) | Prenatal + postnatal, 5.5 months (including 4 months pre-gestation) | - | No significant effect of maternal diet on offspring hypothalamus or olfactory bulb metabolite levels | Safi-Stibler et al., 2020 [20] |
| Rat (Sprague Dawley) | Grandmaternal HFD (60% kcal fat) vs. CD (10% kcal fat) | Prenatal + postnatal, 14 weeks (including 8 weeks pre-gestation) | ↑ anxiety in female F2 offspring in EPM | ↑ hippocampal CRH-R2 in male HFD F2 offspring; ↑ NR3C2 in female HFD F2 offspring | Winther et al., 2019 [21] |
HFD, high fat diet; CD, control diet; PND, postnatal day; OFT, open field test; FST, forced swim test; EPM, elevated plus maze; MWM, Morris water maze; PFC, prefrontal cortex; ZIF-268 encodes zinc finger protein 268 (early growth response protein 1); SYP encodes synaptophysin; CD11b encodes integrin alpha M; TLR4 encodes toll-like receptor 4; IL, interleukin; TPH2 encodes tryptophan hydroxylase; 5-HT1AR encodes the serotonin 1A receptor; BDNF encodes brain-derived neurotrophic factor; CRH encodes corticotropin releasing hormone; NR3C1 encodes the glucocorticoid receptor; AIF1 encodes allograft inflammatory factor 1; TLR9 encodes toll-like receptor 9; CRH-R2 encodes corticotropin-releasing hormone receptor 2; NR3C2 encodes the mineralcorticoid receptor.