Gonadal hormone-dependent vs. -independent effects of kisspeptin signaling in the control of body weight and metabolic homeostasis

Velasco, Inmaculada; León, Silvia; Barroso, Alexia; Ruíz-Pino, Francisco; Heras, Violeta; Torres, Encarnacion; León, María Clemente; Ruohonen, Suvi T.; García-Galiano, David; Romero-Ruíz, Antonio; Sánchez-Garrido, Miguel A.; Olhsson, Claes; Castellano, Juan Manuel Parreño; Roa, Juan; Poutanen, Matti; Pinilla, Leonor; Vázquez, María J.; Tena‐Sempere, Manuel

doi:10.1016/j.metabol.2019.06.007

Cited by 41 publications

(56 citation statements)

References 47 publications

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“…Thus, directly or indirectly, ARN KISS neurones are able to suppress the activity of AgRP/NPY neurones. This has contributed to the idea that kisspeptin itself may have a role in regulating energy balance, 39 although the direct impact of kisspeptin on body weight may be minor compared to kisspeptin‐dependent changes in gonadal hormone levels 40 . Although no single input is likely to have any dominant effect upon the firing of a neurone, current data suggest the existence of a curious reciprocal inhibitory relationship between AgRP/NPY and ARN KISS neurone populations, with each inhibiting the other.…”

Section: Discussionmentioning

confidence: 82%

Direct inhibition of arcuate kisspeptin neurones by neuropeptide Y in the male and female mouse

Hessler

Liu

Herbison

2020

J Neuroendocrinology

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| INTRODUC TI ONThere is a well-recognised relationship between energy status and reproduction, with either under-or over-nutrition being detrimental to fertility. 1 However, the mechanisms and pathways through which energy status suppresses the pulsatile release of luteinising hormone (LH) and gonadotrophin-releasing hormone (GnRH) remain incompletely understood. A wide variety of metabolic hormones and metabolites are implicated in modulating the frequency of the GnRH pulse generator and it is likely that multiple pathways operate in unison to achieve the appropriate pulsatile output for the nutritional status of the animal. 2,3 Foremost amongst these pathways, however, is that involving the arcuate nucleus pro-opiomelanocortin (POMC) and agouti-related peptide/neuropeptide Y (AgRP/NPY) neuronal populations that operate as metabolic sensors to control energy intake and expenditure, as well as fertility. 1,3,4 Abstract Adverse energy states exert a potent suppressive influence on the reproductive axis by inhibiting the pulsatile release of gonadotrophin-releasing hormone and luteinising hormone. One potential mechanism underlying this involves the metabolic-sensing pro-opiomelanocortin and agouti-related peptide/neuropeptide Y (AgRP/NPY) neuronal populations directly controlling the activity of the arcuate nucleus kisspeptin neurones comprising the gonadotrophin-releasing hormone pulse generator. Using acute brain slice electrophysiology and calcium imaging approaches in Kiss1-GFP and Kiss1-GCaMP6 mice, we investigated whether NPY and α-melanocyte-stimulating hormone provide a direct modulatory influence on the activity of arcuate kisspeptin neurones in the adult mouse. NPY was found to exert a potent suppressive influence upon the neurokinin B-evoked firing of approximately one-half of arcuate kisspeptin neurones in both sexes. This effect was blocked partially by the NPY1R antagonist BIBO 3304, whereas the NPY5R antagonist L152,804 was ineffective.NPY also suppressed the neurokinin B-evoked increase in intracellular calcium levels in the presence of tetrodotoxin and amino acid receptor antagonists, indicating that the inhibitory effects of NPY are direct on kisspeptin neurones. By contrast, no effects of α-melanocyte-stimulating hormone were found on the excitability of arcuate kisspeptin neurones. These studies provide further evidence supporting the hypothesis that AgRP/NPY neurones link energy status and luteinising hormone pulsatility by demonstrating that NPY has a direct suppressive influence upon the activity of a subpopulation of arcuate kisspeptin neurones. K E Y W O R D SGCaMP, GnRH, kisspeptin, neuropeptide Y, NPY receptor

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Section: Discussionmentioning

confidence: 82%

Direct inhibition of arcuate kisspeptin neurones by neuropeptide Y in the male and female mouse

Hessler

Liu

Herbison

2020

J Neuroendocrinology

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“…An important factor in the metabolic role of Kiss1 neurons relates to how much of the metabolic phenotype described to date in the different animal models is mediated by kisspeptin vs kisspeptin co-transmitters, for example, glutamate or NKB. In this context, it is worth noting that the degree of obesity observed in the Kiss1 ARC -silenced female mice (57) is significantly greater, and develops faster, than that reported in Kiss1rKO mice (43,44,45,63), supporting a role for additional factors from Kiss1 ARC neurons in the control of metabolism. Importantly, glutamate has been described to mediate the effect (excitation) that Kiss1 ARC neurons exert on POMC neurons, and to selectively inhibit AgRP neurons (10,64), which strongly supports a glutamatergic component in the phenotype of the Kiss1 ARC silenced mouse model (57).…”

Section: Kiss1 Neurons Display Bidirectional Interactions With Agrp Amentioning

confidence: 79%

“…This indicates that a large component of the phenotype observed in adult Kiss1rKO mice is sex-steroid dependent. However, these mice still displayed increased insulin resistance at any age compared to controls suggesting the existence of kisspeptin-dependent mechanism in glucose homeostasis (45).…”

Section: Kiss1 Neurons As Active Metabolic Playersmentioning

confidence: 88%

“…As previously mentioned, a number of studies documented that mice lacking kisspeptin signaling present impaired glucose tolerance that is not exclusively derived from their increased body weight. Both standard chow fed and high fat diet (HFD) fed Kiss1rKO female mice displayed significant glucose intolerance after a glucose tolerance test (GTT) (43,45). This effect was (1) age dependent as adult, but not young 6-week-old, Kiss1rKO females displayed glucose intolerance (63), and (2) sexually dimorphic, as Kiss1rKO males displayed normal basal glucose levels and normal glucose tolerance both under standard chow and HFD (43,45).…”

Section: Glucose Homeostasis Regulation Through Kisspeptin Pathwaysmentioning

confidence: 99%

“…Both standard chow fed and high fat diet (HFD) fed Kiss1rKO female mice displayed significant glucose intolerance after a glucose tolerance test (GTT) (43,45). This effect was (1) age dependent as adult, but not young 6-week-old, Kiss1rKO females displayed glucose intolerance (63), and (2) sexually dimorphic, as Kiss1rKO males displayed normal basal glucose levels and normal glucose tolerance both under standard chow and HFD (43,45). Moreover, this effect in females is exacerbated in the absence of sex steroids, that is, in OVX Kiss1rKO females (43).…”

Section: Glucose Homeostasis Regulation Through Kisspeptin Pathwaysmentioning

confidence: 99%

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Novel insights into the metabolic action of Kiss1 neurons

Talbi

Navarro

2020

Endocrine Connections

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Kiss1 neurons are essential regulators of the hypothalamic–pituitary–gonadal (HPG) axis by regulating gonadotropin-releasing hormone (GnRH) release. Compelling evidence suggests that Kiss1 neurons of the arcuate nucleus (Kiss1ARC), recently identified as the hypothalamic GnRH pulse generator driving fertility, also participate in the regulation of metabolism through kisspeptinergic and glutamatergic interactions with, at least, proopiomelanocortin (POMC) and agouti-related peptide (AgRP)/neuropeptide Y (NPY) neurons, located in close apposition with Kiss1ARC. This review offers a comprehensive overview of the recent developments, mainly derived from animal models, on the role of Kiss1 neurons in the regulation of energy balance, including food intake, energy expenditure and the influence of circadian rhythms on this role. Furthermore, the possible neuroendocrine pathways underlying this effect, and the existing controversies related to the anorexigenic action of kisspeptin in the different experimental models, are also discussed.

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The effects of kisspeptin-type neuropeptides on feeding behavior and intestinal metabolism in the sea cucumber, Apostichopus japonicus

2023

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Gonadal hormone-dependent vs. -independent effects of kisspeptin signaling in the control of body weight and metabolic homeostasis

Cited by 41 publications

References 47 publications

Direct inhibition of arcuate kisspeptin neurones by neuropeptide Y in the male and female mouse

Direct inhibition of arcuate kisspeptin neurones by neuropeptide Y in the male and female mouse

Novel insights into the metabolic action of Kiss1 neurons

The effects of kisspeptin-type neuropeptides on feeding behavior and intestinal metabolism in the sea cucumber, Apostichopus japonicus

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