Role of central kisspeptin and RFRP‐3 in energy metabolism in the male Wistar rat

Cázarez-Márquez, Fernando; Eliveld, Jitske; Ritsema, Wayne I G R; Foppen, Ewout; Bossenbroek, Yvonne; Pelizzari, Simone; Simonneaux, Valérie; Kalsbeek, Andries

doi:10.1111/jne.12973

Cited by 14 publications

(5 citation statements)

References 58 publications

(130 reference statements)

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“…Intriguingly, since insulin is able to relay information regarding body fat status to the central nervous system (reviewed by: 248 , 249 ), inhibition via GnIH further supports a multipronged impact through which GnIH promotes fat accumulation and an elevation in body weight, associated with increased feed intake (see previous section). Furthermore, kisspeptin has also been reported to stimulate glucose production with an increased glucose tolerance to prevent the onset of hyperglycemic disorders ( 250 ) via its receptor. As this effect is absent in GPR54-KO mice ( 251 ), it is possible that cross-activation by various members of the RFamide family, including GnIH, can occur.…”

Section: Beyond Neuroendocrine Functions Gnih and Its Receptor Participate In The Peripheral Regulation Of Physiological Processesmentioning

confidence: 99%

Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction

2022

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Since its discovery as a novel gonadotropin inhibitory peptide in 2000, the central and peripheral roles played by gonadotropin-inhibiting hormone (GnIH) have been significantly expanded. This is highlighted by the wide distribution of its receptor (GnIH-R) within the brain and throughout multiple peripheral organs and tissues. Furthermore, as GnIH is part of the wider RF-amide peptides family, many orthologues have been characterized across vertebrate species, and due to the promiscuity between ligands and receptors within this family, confusion over the nomenclature and function has arisen. In this review, we intend to first clarify the nomenclature, prevalence, and distribution of the GnIH-Rs, and by reviewing specific localization and ligand availability, we propose an integrative role for GnIH in the coordination of reproductive and metabolic processes. Specifically, we propose that GnIH participates in the central regulation of feed intake while modulating the impact of thyroid hormones and the stress axis to allow active reproduction to proceed depending on the availability of resources. Furthermore, beyond the central nervous system, we also propose a peripheral role for GnIH in the control of glucose and lipid metabolism at the level of the liver, pancreas, and adipose tissue. Taken together, evidence from the literature strongly suggests that, in fact, the inhibitory effect of GnIH on the reproductive axis is based on the integration of environmental cues and internal metabolic status.

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Section: Beyond Neuroendocrine Functions Gnih and Its Receptor Participate In The Peripheral Regulation Of Physiological Processesmentioning

confidence: 99%

Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction

2022

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“…Recently, our studies and other previous studies have confirmed that GnIH is involved in this physiological phenomenon. In rodents, Moriwaki et al [29] and Cazarez-Marquez et al [30] found that, although an intracerebral injection of GnIH increased endogenous glucose levels, serum lipid and insulin levels did not change. However, our previous studies revealed that intraperitoneally injected GnIH not only increased food intake and body mass but also induced dyslipidemia and hyperglycemia by causing changes in meal microstructure in rodents and piglets [7][8][9].…”

Section: Discussionmentioning

confidence: 99%

Peripheral 5-HT Mediates Gonadotropin-Inhibitory Hormone-Induced Feeding Behavior and Energy Metabolism Disorder in Chickens via the 5-HT2C Receptor

Song,

Xu,

et al. 2024

Neuroendocrinology

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Gonadotropin-inhibitory hormone (GnIH) plays a critical role of reproduction in vertebrate since its discovery. Recently, a regulatory role of GnIH in appetite and the energy metabolism has emerged, despite its precise physiological mechanisms remain unknown. Thus, the present study evaluated the effects of a single or long-term GnIH treatments (administered via intraperitoneal injection) on the food intake, weight and glucolipid metabolism of chickens, while investigated the possible neuroendocrinology factors and its mechanism that involved in GnIH-induced obesity and glucolipid metabolism disorder. Our results showed that the intraperitoneal administration of GnIH to chickens resulted in marked body mass increased, hyperlipidemia, hyperglycemia and glucose intolerance. Subsequently, the results of metabolomics and pharmacological inhibition of 5-HT2C receptor studies revealed that blocked 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight and the levels of blood glucose and lipid, resulted in GnIH-induced hyperglycaemia, hyperlipidemia and hepatic lipid deposition even worse, suggesting that peripheral 5-HT via 5-HT2C receptor may act as a negative feedback regulator to interplay with GnIH and jointly homeostatic control of energy balance in chickens. Our present study provide evidence of the cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level and to propose a molecular basis for these interactions, suggesting that functional interaction between GnIH and 5-HT may open new avenues to understand the mechanism of neuroendocrine network involved in appetite and energy metabolism as well as provide a new therapeutic strategy to prevent obesity, diabetes and metabolic disorders.

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“…These neuropeptides act through five G protein-coupled receptors (GPCRs): pyroglutamine RF-amide peptide receptor (QRFPR, GPR103) 4 , neuropeptide FF receptor 1/2 (NPFF 1/2 R, GPR147/GPR74) 5 , prolactin-releasing peptide receptor (PrRPR, GPR10) 6 , and kisspeptin receptor (KISS1R, GPR54) 7 . These RF-amide peptides and their respective receptors play crucial roles in a wide range of neuroendocrine and behavioral functions, like modulation of feeding 8 , energy expenditure 9 , 10 , reproduction 11 – 14 , nociception 15 , and cardiovascular regulation 8 .…”

Section: Introductionmentioning

confidence: 99%

Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor

Jin,

Guo,

et al. 2024

Cell Discov

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The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the Gq-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors.

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Role of central kisspeptin and RFRP‐3 in energy metabolism in the male Wistar rat

Cited by 14 publications

References 58 publications

Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction

Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction

Peripheral 5-HT Mediates Gonadotropin-Inhibitory Hormone-Induced Feeding Behavior and Energy Metabolism Disorder in Chickens via the 5-HT2C Receptor

Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor

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