title: Fasting induced kisspeptin signaling suppression is regulated by glutamate mediated cues in adult male rhesus macaque (Macaca mulatta).
abstract: Kisspeptin signaling is suppressed by short term fasting. It has been reported that hypothalamic Kiss1 and Kiss1r mRNA expression decreased after 48h of fasting in male rhesus monkey. But the mechanism involved in the reduction of kisspeptin signaling after 48h of fasting is unknown. Recent studies have suggested the role of afferent excitatory and inhibitory pathways in the regulation of kisspeptin neurons. Therefore, this study was designed to observe the changes in the glutamate and GABA signaling during fed and 48h fasting states by performing immunofluorescence to examine the interaction of kisspeptin neurons with NR1 subunit of NMDA receptors and by performing SYBR green qRT-PCR to measure and quantify the levels of Kiss1, Kiss1r, NR1 and GAD67 mRNA in the POA and MBH of adult male rhesus macaque (Macaca mulatta) during 48h of fasting (n=2) and fed ad libitum (n=2). Plasma testosterone (p<0.05) and blood glucose levels were significantly (p<0.001) decreased after short term fasting. Our results clearly showed that expression of hypothalamic Kiss1, Kiss1r and NR1 mRNA was significantly (p<0.05) reduced in adult male rhesus monkeys which were fasted for 48h as compared to those which were fed ad libitum. There was no clear difference in the GAD67 mRNA contents between the two groups. Number of kisspeptin neurons and the interactions of kisspeptin neurons with NR1 were significantly (p<0.05) reduced after 48h fasting. These observations suggest that decreased kisspeptin signaling during fasting may occur due to reduction in glutamatergic inputs to kisspeptin neurons. Our results also suggest that fasting induced suppression of kisspeptin signaling is not mediated through GABAergic neurons.
authors.affiliation: Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Shazia
authors.initials: S
authors.lastname: Shamas
authors.affiliation: Department of Pathology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
authors.forename: Saeed-Ul-Hassan
authors.initials: SU
authors.lastname: Khan
authors.affiliation: Department of Pathology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
authors.forename: Muhammad Yousaf
authors.initials: MY
authors.lastname: Khan
authors.affiliation: Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Nadia
authors.initials: N
authors.lastname: Shabbir
authors.affiliation: Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Hira
authors.initials: H
authors.lastname: Zubair
authors.affiliation: Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Saira
authors.initials: S
authors.lastname: Shafqat
authors.affiliation: Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Fazal
authors.initials: F
authors.lastname: Wahab
authors.affiliation: Laboratory of Reproductive Neuroendocrinology, Department of Animal Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address: shahab@qau.edu.pk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahab
mesh_terms: D000818:Animals; D001786:Blood Glucose; D003463:Cues; D005215:Fasting / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism*; D059648:Kisspeptins / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D009474:Neurons / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D059648:Kisspeptins; C409466:NR1 NMDA receptor; D043562:Receptors, G-Protein-Coupled; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: Fasting; Glutamate; Kisspeptin; Rhesus macaque