High-Fat Diet Increases LH Pulse Frequency and Kisspeptin-Neurokinin B Expression in Puberty-Advanced Female Rats

To investigate whether the advancement of puberty in response to high-fat diet (HFD) results from a concomitant increase in LH pulse frequency and kisspeptin (Kiss1) and neurokinin B (NKB) signaling in the hypothalamus, blood samples were collected on postnatal day (pnd) 28, 32, or 36 for LH measurement and vaginal opening monitored as a marker of puberty in female rats fed with HFD or standard chow from weaning. Quantitative RT-PCR was used to determine Kiss1 and kisspeptin receptor (Kiss1r) mRNA levels in brain punches of the medial preoptic area and the arcuate nucleus (ARC), and NKB and NKB receptor (NK3R) mRNA levels in the ARC. There was a gradual increase in LH pulse frequency from pnd 28, reaching significance by pnd 36 in control diet-fed rats. The advancement of puberty by approximately 6 d (average pnd 34) in rats fed HFD was associated with an earlier onset of the higher LH pulse frequency that was already extant on pnd 28. The increased levels of expression of Kiss1 in the medial preoptic area and ARC, and NKB in the ARC, associated with pubertal onset were similarly advanced in HFD-fed rats. These data suggest that the earlier accelerated GnRH pulse generator frequency and advanced puberty with obesogenic diets might be associated with premature up-regulation of kisspeptin and NKB signaling in the hypothalamus of the female rat. (Endocrinology 153: 4422-4431, 2012)