Feeding prepubescent gilts a high-fat diet induces molecular changes in the hypothalamus-pituitary-gonadal axis and predicts early timing of puberty

Abstract

Objective

The onset of puberty in females has been occurring earlier over the past decades, presumably as a result of improved nutrition in developed countries. However, the underlying molecular mechanisms responsible for the early attainment of puberty as a result of nutrition fortification remain largely unknown. The aim of this study was to evaluate the hormone and gene expression changes in prepubescent gilts fed a high-fat diet to investigate whether these changes could predict the early timing of puberty.

Methods

Forty gilts were fed a daily basal diet (LE) or a basal diet with an additional 270 g/d or 340 g/d of fat (HE) during the prepubescent phase. Blood samples were collected during the prepubescent phase to detect hormone secretion changes in insulin-like growth factor-1, kisspeptin, estradiol, progesterone, and leptin. The gene expressions at the hypothalamus–pituitary–gonadal axis were examined on day 73 of the experiment (average age on day 177) during the prepubescent phase.

Results

An HE diet resulted in accelerated body weight gain and back-fat thickness at the P₂ point compared with LE gilts during the prepubescent phase. Gilts that were fed HE diets attained puberty 12 d earlier than LE gilts, and a larger proportion of HE gilts reached puberty at day 180 or 190 of age. A postmortem analysis revealed a promoted development of the uterus and ovary tissue that was characterized by a 53.7% and 29.5% increase in the uterine and ovary weight, respectively, and an increased length of the uterine horn and oviduct tissue in HE gilts. Real-time quantitative polymerase chain reaction revealed that HE gilts had higher Kiss-1, G protein-coupled receptor 54, gonadotropin-releasing hormone and estrogen receptor α mRNA expression levels in the hypothalamic anteroventral periventricular nucleus; the leptin receptor mRNA expression level was higher in the hypothalamic arcuate nucleus and ovary tissue; the insulin-like growth factor-1 receptor expression was higher in the pituitary and ovary tissues, and the follicle-stimulating hormone and luteinizing hormone mRNA expression levels were higher in the pituitary gland.

Conclusion

These data showed that the consumption of additional fat can facilitate early attainment of puberty, which can be predicted by the changes in secreted hormones and gene expression in the hypothalamus-pituitary-gonadal axis.

Introduction

The onset of puberty in females, as measured by the age at menarche, is estimated to have advanced by 6 to 12 mo per 100 y between the 18th and 21st centuries in several northern European countries [1]. This declining age of puberty has been attributed to accelerated growth resulting from improved nutrition, e.g., obese girls tend to mature earlier than normal or thin girls [2], [3], [4]. Thus, the accelerated growth rate due to nutrition fortification seems to be a more important index in predicting the early onset of puberty [5]. Although body condition and the timing of puberty show a strong link in developing girls, the underlying mechanism remains largely unknown.

Puberty is a complex biological process that involves the secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus, sexual development, adrenal maturation, pubertal development, and gametogenesis. Notably, the secretion of GnRH by the hypothalamus represents the first known step in the reproductive cascade to initiate the activation of pituitary and gonadal function. Therefore, understanding the neuroendocrine control of GnRH secretion may provide insight into the normal reproduction or disorder of the pubertal process. Recently, pharmacologic and genetic studies revealed that GPR54, a G protein-coupled receptor gene, may act as a gatekeeper for normal GnRH physiology and puberty [6]. Kisspeptins, which are encoded by the metastasis suppressor gene Kiss-1, are a natural ligand for GPR54 to elicit a GnRH surge and puberty onset [7], [8]. Kiss-1 and GPR54 may be involved in the early timing of puberty due to accelerated growth. Thus, their gene expression levels represent an interesting research topic.

In the present study, developing gilts were fed an oil-rich diet to induce hormone and molecular changes in the hypothalamus, pituitary, and gonadal tissues. These changes were used to assess whether hormone and molecular changes could predict the early onset of puberty.