Maternal and postweaning obesity alters regulation of the hypothalamo-pituitary adrenal axis in mature adult mice

Poore, Kirsten, Ogawa, N.O., Teeling, Jessica, Cagampang, Felino, Green, Lucy and Rasool, Aisha (2019) Maternal and postweaning obesity alters regulation of the hypothalamo-pituitary adrenal axis in mature adult mice. XIth World DOHaD Congress, , Melbourne, Australia. 22 - 26 Oct 2019.

Abstract

Background/Aims: Obesity is a major risk factor for non-communicable diseases, including psychiatric disorders such as anxiety. This may be due to altered hypothalamo-pituitary adrenal function. However, we showed previously that anxiety in young adult life was not affected by a maternal or post-weaning obesogenic high fat (HF) diet. Here we examined the effect of these HF diets on anxiety in mature adult life and related it to adrenal morphology. 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 (CC: n=8-10; CHF: n=4-12; HFC: n=9-12; HFHF: n=7-8/sex). In 52-week offspring, anxiety markers (distance travelled in centre [DTC] and entries to centre [EC]; open field test) and basal plasma ACTH concentrations (ELISA) were measured. Adrenal glands, cortex area, nuclei density (H&E) and lipid content (Oil Red O) were measured (ImageJ). Data were analysed by mixed effects model (SPSS). Results: In males and females, maternal HF and postweaning HF diet increased anxiety (reduced DTC: maternal P<0.05, postweaning P<0.01; reduced EC: postweaning P<0.001). Postweaning HF diet increased cortex area in males and females (P<0.01, P<0.001, respectively), without any change in nuclei density. In females only, postweaning HF diet increased basal ACTH concentrations (P<0.01) and adrenal lipid content (P<0.05). Maternal HF diet did not affect offspring adrenal cortex area or lipid content. Conclusions: These finding suggest that maternal and postweaning HF diet increase the risk of anxiety, which becomes apparent with advancing age. Postweaning, but not maternal, HF diet was associated with expansion of the adrenal cortex due to hyperplasia. This could contribute to the elevated basal corticosterone we previously observed in these animals and to their anxiety. In females, the increase in adrenal cortex area following postweaning HF diet could be driven by elevated ACTH concentrations and was associated with adrenal lipid content, which may impair normal adrenal function

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Contributors

Author: Kirsten Poore

Author: Jessica Teeling

Author: Felino Cagampang

Author: Lucy Green

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