AbstractKisspeptins are essential regulators of the reproductive axis, with capacity to potently activate gonadotropin‐releasing hormone neurons, acting also as central conduits for the metabolic regulation of fertility. Recent evidence suggests that kisspeptins per se may also modulate several metabolic parameters, including body weight, food intake or energy expenditure, but their actual roles and site(s) of action remain unclear. We present herein a series of studies addressing the metabolic effects of central and peripheral administration of kisspeptin‐10 (Kp‐10; 1 nmol and 3 nmol daily, respectively) for 11 days in mice of both sexes. To assess direct metabolic actions of Kp‐10 versus those derived indirectly from its capacity to modulate gonadal hormone secretion, kisspeptin effects were tested in adult male and female mice gonadectomized and supplemented with fixed, physiological doses of testosterone or 17β‐estradiol, respectively. Central administration of Kp‐10 decreased food intake in male mice, especially during the dark phase (~50%), which was accompanied by a reduction in total and nocturnal energy expenditure (~16%) and locomotor activity (~70%). In contrast, opposite patterns were detected in female mice, with an increase in total and nocturnal locomotor activity (>65%), despite no changes in food intake or energy expenditure. These changes were independent of body weight, as no differences were detected in mice of both sexes at the end of Kp‐10 treatments. Peripheral administration of Kp‐10 failed to alter any of the metabolic parameters analyzed, except for a decrease in locomotor activity in male mice and a subtle increase in 24 h food intake in female mice, denoting a predominant central role of kisspeptins in the control of energy metabolism. Finally, glucose tolerance and insulin sensitivity were not significantly affected by central or peripheral treatment with Kp‐10. In conclusion, our data reveal a potential role of kisspeptins in the control of key metabolic parameters, including food intake, energy expenditure and locomotor activity, with a preferential action at central level, which is sex steroid‐independent but sexually dimorphic.

07 Aug 2024·ACS Chemical Neuroscience

Native Mass Spectrometry-Centric Approaches Revealed That Neuropeptides Frequently Interact with Amyloid-β

Article

Author: Wang, Xiankun ; Wang, Guibin ; Jia, Chenxi ; Ren, Zhenhua ; Wang, Danyang

Amyloid-β (Aβ) aggregates are recognized as initiators of Alzheimer's disease, and their interaction with the nervous system contributes to the progression of neurodegeneration. Herein, we investigated the frequency at which neuropeptides interact with Aβ and affect the aggregation kinetics and cytotoxicity of Aβ. To this end, we established a native mass spectrometry (MS)-centric workflow for screening Aβ-interacting neuropeptides, and six out of 12 neuropeptides formed noncovalent complexes with Aβ species in the MS gas phase. Thioflavin-T fluorescence assays and gel separation indicated that leptin and cerebellin decreased Aβ aggregation, whereas kisspeptin increased this process. In addition, leptin and cerebellin attenuated Aβ-induced cytotoxicity, which was independent of the influence of metal ions. Leptin can chelate copper from copper-bound Aβ species, reducing the cytotoxicity caused by the aggregation of Aβ and metal ion complexes. Overall, our study demonstrated that neuropeptides frequently interact with Aβ and revealed that leptin and cerebellin are potential inhibitors of Aβ aggregation, providing great insight into understanding the molecular mechanism of Aβ interacting with the nervous system and facilitating drug development.

01 Aug 2024·Metabolism

The evolutionary conserved miR-137/325 tandem mediates obesity-induced hypogonadism and metabolic comorbidities by repressing hypothalamic kisspeptin

Article

Author: Tena-Sempere, Manuel ; Pineda, Rafael ; Sobrino, Verónica ; Guerrero-Ruiz, Yolanda ; Ruiz-Pino, Francisco ; Ruiz-Cruz, Miguel ; Lara-Chica, Maribel ; García-Redondo, Ana B ; Fernandez-Garcia, José C ; Vázquez, María J ; Avendaño, María S ; Garcia-Galiano, David ; Perdices-Lopez, Cecilia ; Barroso, Alexia ; Pitteloud, Nelly ; Hernanz, Raquel ; Calzado, Marco A ; Rodriguez-Sanchez, Ana B ; Briones, Ana M ; Sanchez-Tapia, María J ; Correa-Sáez, Alejandro

BACKGROUNDObesity-induced hypogonadism (OIH) is a prevalent, but often neglected condition in men, which aggravates the metabolic complications of overweight. While hypothalamic suppression of Kiss1-encoded kisspeptin has been suggested to contribute to OIH, the molecular mechanisms for such repression in obesity, and the therapeutic implications thereof, remain unknown.METHODSA combination of bioinformatic, expression and functional analyses was implemented, assessing the role of the evolutionary-conserved miRNAs, miR-137 and miR-325, in mediating obesity-induced suppression of hypothalamic kisspeptin, as putative mechanism of central hypogonadism and metabolic comorbidities. The implications of such miR-137/325-kisspeptin interplay for therapeutic intervention in obesity were also explored using preclinical OIH models.RESULTSMiR-137/325 repressed human KISS1 3'-UTR in-vitro and inhibited hypothalamic kisspeptin content in male rats, while miR-137/325 expression was up-regulated, and Kiss1/kisspeptin decreased, in the medio-basal hypothalamus of obese rats. Selective over-expression of miR-137 in Kiss1 neurons reduced Kiss1/ kisspeptin and partially replicated reproductive and metabolic alterations of OIH in lean mice. Conversely, interference of the repressive actions of miR-137/325 selectively on Kiss1 3'-UTR in vivo, using target-site blockers (TSB), enhanced kisspeptin content and reversed central hypogonadism in obese rats, together with improvement of glucose intolerance, insulin resistance and cardiovascular and inflammatory markers, despite persistent exposure to obesogenic diet. Reversal of OIH by TSB miR-137/325 was more effective than chronic kisspeptin or testosterone treatments in obese rats.CONCLUSIONSOur data disclose that the miR-137/325-Kisspeptin repressive interaction is a major player in the pathogenesis of obesity-induced hypogonadism and a putative druggable target for improved management of this condition and its metabolic comorbidities in men suffering obesity.SIGNIFICANCE STATEMENTUp to half of the men suffering obesity display also central hypogonadism, an often neglected complication of overweight that can aggravate the clinical course of obesity and its complications. The mechanisms for such obesity-induced hypogonadism remain poorly defined. We show here that the evolutionary conserved miR137/miR325 tandem centrally mediates obesity-induced hypogonadism via repression of the reproductive-stimulatory signal, kisspeptin; this may represent an amenable druggable target for improved management of hypogonadism and other metabolic complications of obesity.

100 Deals associated with Kisspeptin(Shangpharma Corp.)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus	Preclinical	CN	Shangpharma Corp.	16 Sep 2022
Infertility	Preclinical	CN	Shangpharma Corp.	16 Sep 2022
Neoplasms	Preclinical	CN	Shangpharma Corp.	16 Sep 2022
Sexual Dysfunction	Preclinical	CN	Shangpharma Corp.	16 Sep 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Kisspeptin(Shangpharma Corp.)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation