The role of adrenal morphology in high fat diet-induced anxiety in mature adult mice

Poore, Kirsten, Green, Lucy, Cagampang, Felino, Teeling, Jessica, Rasool, Aisha and Ogawa, N.O. (2019) The role of adrenal morphology in high fat diet-induced anxiety in mature adult mice. XIth World DOHaD Congress, , Melbourne, Australia. 22 - 26 Oct 2019.

Abstract

Background/Aims: We have shown effects of both maternal and postweaning HF diet-induced obesity to increase anxiety and corticosterone output in mature adult mice, suggesting changes in the regulation of the hypothalamo-pituitary adrenal (HPA) axis. The current study investigated glucocorticoid (GR) and mineralocorticoid (MR) receptors in key brain regions of these mice, as well as FKBP51, a negative modulator of these receptors that is associated with anxiety-related disorders. Method: Female C57BL/6 mice were fed either HF (HF: 45% kcal fat) or control diet (C: 7% kcal fat) 6 weeks before mating and throughout pregnancy and lactation. Male and female offspring were fed C or HF diet from weaning (3 weeks) (CC: n=7-8; CHF: n=4-7; HFC: n=7-9; HFHF: n=6-8/sex). In 52-week offspring brain (hippocampus [CA3] and hypothalamus [PVN]), GR, MR and FKBP51 mRNA levels were measured (RT-PCR). Data were analysed by mixed effects model (SPSS). Results: In 52 week males, maternal HF diet reduced MR (P<0.001) and increased FKBP51 (P<0.01) in CA3. Postweaning HF diet also increased FKBP51 (P<001) in CA3 in males. In females, postweaning HF diet reduced MR (P<0.01) in CA3 but increased MR (P<0.05) and FKBP51 (P<0.001) in PVN. GR was unaffected in either sex by maternal or postweaning HF diet in PVN or CA3. Conclusions: Changes in key factors in feedback mechanisms of the HPA axis in the mature adult brain suggest that maternal and postweaning HF diets may have long-term effects on stress responsiveness in a sex-specific manner. The increase in FKBP51 in both males and females following postweaning HF diet could be linked to the increased basal corticosterone we have previously observed in these animals, contributing to their heightened anxiety.

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Contributors

Author: Kirsten Poore

Author: Lucy Green

Author: Felino Cagampang

Author: Jessica Teeling

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