Emerging roles of kisspeptin/galanin in age-related metabolic disease

Fang, Penghua; She, Yuqing; Zhao, Juan; Yan, Jing; Yu, Xizhong; Jin, Yu; Wei, Qingbo; Zhang, Zhenwen; Shang, Wenbin

doi:10.1016/j.mad.2021.111571

Cited by 6 publications

(3 citation statements)

References 106 publications

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“…Unraveling the influence of the kisspeptin-KISS1R axis on these aging-related cellular mechanisms [ 77 ] and their contributions to CKD pathogenesis may hold importance for devising effective preventive and therapeutic strategies to address the mounting burden of CKD in the aging population. Moreover, kisspeptin is believed to play a role in the regulation of metabolism by exerting anti-obesitogenic effects, and its levels are inversely correlated with insulin resistance [ 17 ]. These metabolic pathways also hold significance in the regulation of cellular aging processes.…”

Section: Discussionmentioning

confidence: 99%

“…The 145 amino acid-encoding product of the Kiss1 gene is cleaved into shorter KPs of 54, 14, 13, or 10 amino acids in length [ 21 ]. Plasma levels of these C-terminal cleavage fragments, including KP-54 (formerly known as metastin), KP-14, KP-13, and KP-10, show age dependence [ 17 , 23 , 24 ]. All have biological activity and are the endogenous ligands for the G-protein-coupled receptor GPR54 (i.e., KISS1R) [ 17 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…Plasma levels of these C-terminal cleavage fragments, including KP-54 (formerly known as metastin), KP-14, KP-13, and KP-10, show age dependence [ 17 , 23 , 24 ]. All have biological activity and are the endogenous ligands for the G-protein-coupled receptor GPR54 (i.e., KISS1R) [ 17 , 23 , 24 ]. The kisspeptin-KISS1R system, initially recognized for its role in reproductive physiology, is now known to exert various functions in non-reproductive tissues, including the kidneys.…”

Section: Introductionmentioning

confidence: 99%

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Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy

Dinh,

Kovács,

Kis

et al. 2023

GeroScience

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The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction’s echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory (Il6, Tnf), fibrosis (Col1), and apoptosis markers (Bax/Bcl2) relative to the CKD group. In summary, KP-13’s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle.

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Section: Discussionmentioning

confidence: 99%