# High-fat diet prevents adaptive peripartum-associated adrenal gland plasticity and anxiolysis

## TL;DR

A high-fat diet disrupts normal changes in the adrenal glands during pregnancy and lactation, leading to increased anxiety and stress responses in mothers.

## Contribution

The study reveals that high-fat diets prevent adaptive adrenal gland changes during the peripartum period.

## Key findings

- High-fat diets prevent lactation-associated anxiolysis and basal hypercorticism.
- HFD prevents downregulation of adrenal cholesterol stores and HMGCR expression.
- Adrenal LDLR upregulation at mid-lactation is prevented by HFD.

## Abstract

Maternal obesity is associated with lower basal plasma cortisol levels and increased risk of postpartum psychiatric disorders. Given that both obesity and the peripartum period are characterized by an imbalance between adrenocorticotropic hormone (ACTH) and cortisol, we hypothesized that the adrenal glands undergo peripartum-associated plasticity and that such changes would be prevented by a high-fat diet (HFD). Here, we demonstrate substantial peripartum adrenal gland plasticity in the pathways involved in cholesterol supply for steroidogenesis in female rats. In detail, the receptors involved in plasma lipid uptake, low density lipoprotein (LDL) receptor (LDLR) and scavenger receptor class B type 1 (SRB1), are elevated, intra-adrenal cholesterol stores are depleted, and a key enzyme in de novo cholesterol synthesis, hydroxymethylglutaryl coenzyme A reductase (HMGCR), is downregulated; particularly at mid-lactation. HFD prevented the lactation-associated anxiolysis, basal hypercorticism, and exaggerated the corticosterone response to ACTH. Moreover, we show that HFD prevented the downregulation of adrenal cholesterol stores and HMGCR expression, and LDLR upregulation at mid-lactation. These findings show that the adrenal gland is an important regulator of peripartum-associated HPA axis plasticity and that HFD has maladaptive consequences for the mother, partly by preventing these neuroendocrine and also behavioural changes.