Intermittent Fasting Dietary Restriction Regimen Negatively Influences Reproduction in Young Rats: A Study of Hypothalamo-Hypophysial-Gonadal Axis

Department of Biotechnology, Guru Nanak Dev University, Amritsar, Punjab, India.
PLoS ONE (Impact Factor: 3.23). 01/2013; 8(1):e52416. DOI: 10.1371/journal.pone.0052416
Source: PubMed


Nutritional infertility is very common in societies where women fail to eat enough to match their energy expenditure and such females often present as clinical cases of anorexia nervosa. The cellular and molecular mechanisms that link energy balance and central regulation of reproduction are still not well understood. Peripheral hormones such as estradiol, testosterone and leptin, as well as neuropeptides like kisspeptin and neuropeptides Y (NPY) play a potential role in regulation of reproduction and energy balance with their primary target converging on the hypothalamic median eminence-arcuate region. The present study was aimed to explore the effects of negative energy state resulting from intermittent fasting dietary restriction (IF-DR) regimen on complete hypothalamo-hypophysial-gonadal axis in Wistar strain young female and male rats. Significant changes in body weight, blood glucose, estrous cyclicity and serum estradiol, testosterone and LH level indicated the negative role of IF-DR regimen on reproduction in these young animals. Further, it was elucidated whether serum level of metabolic hormone, leptin plays a mechanistic role in suppressing hypothalamo-hypophysial-gonadal (HPG) axis via energy regulators, kisspeptin and NPY in rats on IF-DR regimen. We also studied the effect of IF-DR regimen on structural remodeling of GnRH axon terminals in median eminence region of hypothalamus along with the glial cell marker, GFAP and neuronal plasticity marker, PSA-NCAM using immunostaining, Western blotting and RT-PCR. Together these data suggest that IF-DR regimen negatively influences reproduction in young animals due to its adverse effects on complete hypothalamus-hypophysial-gonadal axis and may explain underlying mechanism(s) to understand the clinical basis of nutritional infertility.

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    • "Specifically, CR increased the density of NPY-ir material across the rostrocaudal extent of the ARC in vehicle-injected mice, and in all but the most rostral ARC level in LPS-injected mice. This is consistent with previous studies reporting CR-induced enhancement of ARC levels of NPY mRNA expression (Brady et al., 1990; McShane et al., 1999; Shimokawa et al., 2003; Johnstone et al., 2005), NPY protein (Lewis et al., 1993), and NPY-immunolabeling (Abizaid et al., 1997; Kurose et al., 2005; Kumar and Kaur, 2013). Similarly, our laboratory previously found that hypothalamic NPY Fig. 4. Calorie restriction reduced the total area of Iba1-positive microglial cells in the arcuate hypothalamic nucleus (ARC). "
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