Effects of Photoperiod Alteration on the Hypothalamic-Pituitary-Adrenal Stress Axis in Male C57BL/6J Mice and the Impact of Dietary Isoflavones

Presentation Number: MON 373
Date of Presentation: April 3rd, 2017

Bradly M Bauman*1, Robert J Handa2 and T John Wu1
1Uniformed Services University, Bethesda, MD, 2Colorado State University, Fort Collins, CO


The hypothalamic-pituitary-adrenal (HPA) axis functions to regulate the stress response and synchronize physiological systems with environmental cues and rhythms. Neuronal inputs lead to adrenal secretion of corticosterone (CORT), whose release functions to inhibit the HPA axis stress response. In addition, CORT aligns physiological functions such as energy intake, metabolism, motor performance, and cognitive function to the central circadian clock, located in the suprachiasmatic nucleus of the hypothalamus (SCN). The SCN utilizes environmental input such as daylight to entrain peripheral clocks, and various stimuli can impact the HPA axis, leading to an altered stress response. As such, adjusted periods of activity or inactivity (photoperiods) can induce HPA dysregulation, leading to altered metabolism and anxiety- and depressive-like behavior. Similarly, naturally occurring non-steroidal isoflavones, present in soy-based rodent chow, have been shown to exert sex-dependent effects on metabolism and behavior. In the current study, we determined the effect of exposure to a short-day (SD) photoperiod (shortened active period), as well as examined the role of isoflavones, on body weight regulation, CORT response, gene expression relevant to the HPA axis, and serum cytokine levels in mice. Male C57BL/6J mice were fed either soy-based or soy-free diets and acclimated to a normal (12L:12D) photoperiod, after which time they were exposed to either a normal or SD (16L:8D) photoperiod. In soy-fed mice, exposure to a short-day increased the ratio of brown adipose tissue (BAT) to white adipose tissue (WAT) (p < 0.05). Soy-fed mice also gained less weight, independent of photoperiod (p < 0.05). Additionally, soy-fed mice had a lower BAT/WAT ratio in the normal photoperiod (p < 0.05). The effects of photoperiod alteration on the HPA stress response were analyzed by assessing the CORT response to an acute 20 minute restraint stress. Short-day mice displayed increased basal CORT levels independent of diet (p < 0.05). Additionally, exposure to short-day increased basal CORT levels to a greater extent in soy-fed mice (p < 0.05). Among normal day mice, expression of adrenal 11β-HSD1 mRNA, an enzyme crucial to reactivating CORT, was increased in those fed soy-free diets (p < 0.05). Photoperiod and isoflavone effects were also analyzed in serum cytokine levels. After short-day exposure, increased serum levels of MIP-1α and RANTES were seen in mice fed soy-free diets (p < 0.05). In contrast, short-day exposure decreased serum MIP-1α levels soy-fed mice (p < 0.05). Additionally, among normal-day mice, MIP-1α levels were elevated in soy-fed mice (p < 0.05). Our results suggest that exposure to a short-day photoperiod leads to dysregulation of the HPA axis centrally and that the effects are lessened in male mice fed a soy-free diet.


Nothing to Disclose: BMB, RJH, TJW