Effect of a postnatal high-fat diet exposure on puberty onset, estrous cycle regularity, and kisspeptin expression in female rats
Introduction
The time of puberty onset in girls has advanced within the last few decades both in Europe and in US, but the mechanism behind this phenomenon has not yet been elucidated [1], [2], [3]. The increased prevalence of obese children in the same period has drawn attention to a more causal link as epidemiological studies have shown an association between obesity markers in childhood and earlier pubertal maturation in girls [4], [5]. Along the same line, the reproductive function in women is impaired both by a negative [6] and positive nutritional status [7], and the escalating obesity epidemic is believed to be associated with the increased prevalence of reproductive dysfunction in women [7], [8], [9], [10]. In animal models, exposing female rodents to high-fat diet (HFD) during gestation and/or postnatally advanced puberty onset and induced irregular estrous cycles in adult rats [11], [12], [13], [14], [15], [16], [17], [18], [19]. However, like in humans, little is known about the underlying neuroendocrine mechanism of metabolic regulation of pubertal maturation and reproductive function.
Kisspeptin, derived from the Kiss1 gene, plays a key role in pubertal maturation and reproduction in both rodents and humans as an elicitor of gonadotropin-releasing hormone (GnRH) and an upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis [20]. The kisspeptin system, comprised of two neuron populations located in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) in rodents [21], [22], [23], undergoes both neuroanatomical changes and functional activation primarily prior to and around puberty onset [24]. This is accompanied by an enhanced synaptic transmission at the level of the GnRH neurons [24], [25], [26], [27], [28], [29]. Thus, developmental changes in the kisspeptin system are believed to play an important role in the initiation of pubertal maturation and attainment of reproductive function [20], [30].
In recent years, evidence from several lines of research indicate that kisspeptin neurons constitute a conduit for the metabolic regulation of GnRH neurons, a hypothesis based on in vivo findings showing that the kisspeptin system is sensitive to changes in the energy status of the organism [20], [31], [32], [33]. Several studies have documented that a negative energy status reduces the hypothalamic Kiss1 expression in rodents and higher primates [34], [35], [36], [37], whereas a positive energy status has been found to increase hypothalamic Kiss1 expression in female pubertal rats [18], [37] and decrease hypothalamic Kiss1 expression in female adult mice [38]. Thus, the reported effects of a positive energy status on the kisspeptin system are ambiguous. Moreover, the effect of HFD exposure in distinct postnatal periods on the timing of puberty onset and Kiss1/kisspeptin expression has only been studied fragmentarily. Thus, the first aim of this study was to evaluate the effect of HFD exposure during the pre-weaning period, post-weaning period, and in both periods on puberty onset, Kiss1 expression, and number of kisspeptin-immunoreactive (kisspeptin-ir) cells in the AVPV and ARC in peri-pubertal female rats. Also, the role of the kisspeptin system in a metabolic regulation of the estrous cycle in rodents is poorly described. Therefore, the second aim was to examine the link between the regularity of the estrous cycle and changes in Kiss1 expression in the AVPV and ARC in young adult rats exposed to HFD from weaning.
Section snippets
Animals and diets
Female Sprague-Dawley rats (Charles River Laboratories, Sulzfeld, Germany) were housed under conditions of 12 h light/dark cycle (light on at 7:00 am) with free access to water and test diet. The rats were acclimatized 7 days prior to experiments. For experiment 1 and 3, rats were purchased at postnatal day (PND) 14 (9 surrogate dams each with 10 pups). At PND 21 the pups were randomly assigned to the control and HFD groups, balancing for the body weights of the pups. For experiment 2, rats were
Effect of postnatal HFD exposure on body weight and pubertal timing
The effect of HFD exposure during the pre-weaning, post-weaning period, or in both periods on body weight and pubertal timing was examined. Body weight was assessed throughout the HFD exposure periods until sacrifice at PND 34 (Fig. 1A–C). The post-weaning HFD exposure (HFD PND 21–34) increased body weight slightly from PND 28 onwards (Fig. 1A, PND 34; control: 111.2 g ± 1.2 g; HFD PND 21–34: 115.8 g ± 1.0 g), whereas pre-weaning HFD exposure (Fig. 1B, HFD PND 1–16) and HFD exposure from birth (Fig. 1
Puberty onset and the kisspeptin system after postnatal HFD exposure
HFD exposure during the pre-weaning period, post-weaning period, and in both periods had no effect on the timing of puberty onset in female rats in our study. Only rats exposed to HFD during the post-weaning period increased in body weight. The effects of postnatal HFD exposure on pubertal timing have produced ambiguous results. HFD exposure from birth or post-weaning was found to advance puberty onset in female rodents either without affecting body weight [13], [14], [15], [16], [17], [19],
Conflict of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the article reported.
Acknowledgements
This study was supported by the Danish Medical Research Council (09-073164, 2009) and the NOVO Nordisk Foundation.
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2022, Journal of Nutritional BiochemistryCitation Excerpt :These results were consistent with the findings by Maria et al. The report found that postnatal HFD exposure did not affect Kiss1 mRNA expression in the arcuate nucleus and anteroventral periventricular nucleus of female rats in all HFD groups at peri-puberty [36]. In another study, in which HFD induced early puberty onset in the pre-weaning overfeeding model, no significant change was observed in the hypothalamic kisspeptin on VO day [37].
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2020, Cell MetabolismCitation Excerpt :On the contrary, lowering of kisspeptin content may stem from an increase in the release of the peptide. Indeed, hypothalamic expression of Kiss1/kisspeptin is known to increase preferentially in the ARC in different animal models of early overnutrition linked to precocious puberty (Castellano et al., 2011; Lie et al., 2013; Takumi et al., 2015; Ullah et al., 2017; Vazquez et al., 2018). Moreover, opposite conditions of suppressed Kiss1 expression in the hypothalamus, such as lactation, have been shown to lead to accumulation of kisspeptin and increased kisspeptin content in the AVPV, despite suppression of Kiss1 mRNA levels (True et al., 2011).
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2020, Acta HistochemicaCitation Excerpt :Similar to males, alterations in reproductive functions caused by HFD were also seen in females. We (Ziarniak et al., 2018) and others (Balasubramanian et al., 2012; Lie et al., 2013; Ngadjui et al., 2015; Wang et al., 2014) have shown that diet-induced obesity leads to disruptions of the regularity of the estrous cycle. However, severity of these alterations depends on composition of HFD, as well as duration of exposure.