Adult consequences of post-weaning high fat feeding on the limbic-HPA axis of female rats

Abstract

The peripubertal period is critical for the final maturation of circuits controlling energy homeostasis and stress response. However, the consequence of juvenile fat consumption on adult physiology is not clear. This study analyzed the adult consequences of post-weaning fat feeding on limbic-hypothalamic-pituitary-adrenal (HPA) axis components and on metabolic regulators of female rats. Wistar rats were fed either a high fat (HF) diet or the normal chow from weaning to puberty or to 3 months of age. Additional groups crossed their diets at puberty onset. Plasma leptin, insulin, and corticosterone levels were determined by radioimmunoassay and their brain receptors by western blot analysis. Adult HF-fed animals though not overweight, had higher corticosterone and reduced glucocorticoid receptor levels in the hypothalamus and hippocampus, compared to the controls. The alterations in HPA axis emerged already at puberty onset. Leptin receptor levels in the hypothalamus were reduced only by continuous fat feeding from weaning to adulthood. The pre-pubertal period appeared more vulnerable to diet-induced alterations in adulthood than the post-pubertal one. Switching from fat diet to normal chow at puberty onset restored most of the diet-induced alterations in the HPA axis. The corticosteroid circuit rather than the leptin or insulin system appears as the principal target for the peripubertal fat diet-induced effects in adult female rats.

Fig. 1

Effect of fat diet and age on plasma levels of a corticosterone, b insulin, c leptin and d glucose of pubertal and adult female rats fed either the control (C) or the high fat (HF) diet from weaning onwards. Bars represent means ± SEM. # Denotes significant effect of diet on same age groups and $ significant difference between pubertal and adult animals on the same diet. (Two-way ANOVA; significance was accepted for P < 0.05)

Fig. 2

Effect of fat feeding period on adult animals’ corticosterone levels. Female rats were fed either the control (C) diet from weaning to postnatal day 90, or the high fat diet from weaning to postnatal day 90 (HF), or the high fat diet from puberty to postnatal day 90 (C to HF), or the high fat diet from weaning to puberty and then switched to chow (HF to C). Bars represent means ± SEM. * Denotes significant difference from the control diet group. One-way ANOVA followed by Dunnett’s two-sided post hoc test; significance was accepted for P < 0.05

Fig. 3

Effect of diet and age on glucocorticoid receptor (GR) in the hypothalamus (a) and hippocampus (b), on leptin receptor (ObR) in the hypothalamus (c) and on insulin receptor (IR) in the hippocampus (d) of pubertal and adult rats, as depicted by western blot analysis. Female rats were fed either the control (C) or the high fat (HF) diet from weaning onwards. Bars represent means ± SEM of the optical density (OD) of receptors’ band divided by that of the respective actin band in each sample. For insulin receptor, the isoforms IR95 and IR83 were analyzed together. # Denotes significant effect of diet on same age groups and $ significant difference between pubertal and adult animals on the same diet. (Two-way ANOVA; significance was accepted for P < 0.05)

Fig. 4

Effect of fat feeding period on adult animals’ glucocorticoid receptor (GR) in the hypothalamus (a) and hippocampus (b) and on leptin receptor (ObR) in the hypothalamus (c), as depicted by western blot analysis. Female rats were fed either the control (C) diet from weaning to postnatal day 90, or the high fat diet from weaning to postnatal day 90 (HF), or the high fat diet from puberty to postnatal day 90 (C to HF), or the high fat diet from weaning to puberty and then switched to chow (HF to C). Bars represent means ± SEM of the optical density (OD) of receptors’ band divided by that of the respective actin band in each sample. * Denotes significant difference from the control diet group. One-way ANOVA followed by Dunnett’s two-sided post hoc test; significance was accepted for P < 0.05