Effect of leptin on renal ischemia-reperfusion damage in rats

Erkasap, Serdar; Erkasap, Nilüfer; Köken, Tülay; Kahraman, Ahmet; Uzuner, Kubi̇lay; Yazıhan, Nuray; Ateş, Ersin

doi:10.1007/bf03168443

Cited by 33 publications

(34 citation statements)

References 31 publications

(26 reference statements)

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“…24 Leptin-stimulated ROS production and NO synthesis has been shown also to protect against ischemia reperfusion injury in the gut and kidney. 162,163 Clinically, it is interesting to note that patients with a higher body mass index have better outcomes following an acute coronary syndrome or percutaneous coronary intervention. 164,165 Leptin Resistance in the Cardiovascular System?…”

Section: Protection In Ischemia/reperfusion Injurymentioning

confidence: 99%

Leptin Signaling and Obesity

Yang

Barouch

2007

Circulation Research

283

131

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Abstract-Leptin, among the best known hormone markers for obesity, exerts pleiotropic actions on multiple organ systems. In this review, we summarize major leptin signaling pathways, namely Janus-activated kinase/signal transducers and activators of transcription and mitogen-activated protein kinase, including possible mechanisms of leptin resistance in obesity. The effects of leptin on the cardiovascular system are discussed in detail, including its contributions to hypertension, atherosclerosis, depressed myocardial contractile function, fatty acid metabolism, hypertrophic remodeling, and reduction of ischemic/reperfusion injury. The overall goal is to summarize current understanding of how altered leptin signaling in obesity contributes to obesity-related cardiovascular disease. Extensive evidence now supports the notion that maladaptation of the biological system for weight maintenance makes it extremely difficult for people to maintain weight loss. 1 Several genes have been identified to disclose a physiological system that maintains body weight within a range of about twenty pounds. 2 A key element of this system is leptin, the 16-kDa hormonal product of the obesity (ob) gene. 3 Leptin is primarily secreted by adipocytes and is a classic member of the more than 50 identified adipocytokines that participate in adipose tissue hormonal signaling. 4 Since its identification in 1994, leptin has attracted much attention as one of the most important central and peripheral signals for the maintenance of energy homeostasis. [5][6][7][8] For example, a 9-year-old girl with extreme obesity was found to lack leptin. 9 Leptin treatment reduced her weight to the normal range for her age, and the same effects were observed in her similarly affected cousin. 10 Plasma leptin is generally proportional to adipose mass. 11,12 The primary physiological role of leptin is to communicate to the central nervous system (CNS) the abundance of available energy stores and to restrain food intake and induce energy expenditure. The absence of leptin therefore leads to increased appetite and food intake that result in morbid obesity. Notably, only rare cases of severe early childhood obesity have been associated with leptin deficiency. 9,13 The remainder of the obese population typically have elevated leptin levels. 14 The failure of leptin to induce weight loss in these cases is thought to be the result of leptin resistance.Hyperleptinemia, nearly universally observed in human obesity and animal models, is accompanied by a disruption of the usual activities of the hormone, possibly at different Original received May 22, 2007; revision received July 20, 2007; accepted August 6, 2007 18 -20 Obesity is also a part of the metabolic syndrome, which is diagnosed by a set of criteria that include abdominal obesity, insulin resistance, dyslipidemia, and hypertension. This patient population faces increased risk for type 2 diabetes and cardiovascular diseases. The widely distributed Ob-Rs make the hormone an attractive candidate for a molecul...

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Section: Protection In Ischemia/reperfusion Injurymentioning

confidence: 99%

Leptin Signaling and Obesity

Yang

Barouch

2007

Circulation Research

283

131

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“…Our previous studies reported that leptin has a protective effect on renal I/R model induced by 1 hour of ischemia following 1 hour of reperfusion (1). Another study showed the protective effects of resveratrol against oxidative stress on cardiac I/R model in the same time periods (2).…”

Section: Introductionmentioning

confidence: 97%

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats

Erkasap¹,

Erkasap²,

Bradford³

et al. 2017

BLL

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OBJECTIVE: Our study aimed to investigate the possible modifying effects of leptin and combined use of resveratrol on rat renal I/R injury and their relationship on signal pathways and apoptosis-related mechanisms. BACKGROUND: Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal failure. METHODS: Male Sprague Dawley rats were divided into 5 groups: Control, I/R, I/R+leptin, I/R+resveratrol and I/R+leptin+resveratrol. Leptin (10 μg/kg BW) was administered (i.p.) 30 min prior to I/R. Resveratrol was administered by gavage at 20 mg/kg BW per d for 12 d prior to I/R. The left renal artery was exposed to 1 h of ischemia and 1 h of reperfusion. RESULTS: Resveratrol treatment alone increased TNF-α, TNF-α R1, NF-κB, SIRT-1, STAT1 and STAT3 mRNA levels and decreased caspase 3 protein levels. Leptin treatment alone signifi cantly decreased the caspase 3 protein levels. The combined use of resveratrol and leptin signifi cantly increased STAT3, and caspase 3 mRNA levels, and decreased the caspase 3 protein levels. Apoptosis was signifi cantly decreased especially in the leptin and leptin+resveratrol groups. CONCLUSION: The present study suggest that a combined use of resveratrol and leptin has preventive and regulatory effects on renal I/R injury; the mechanism involves decreasing apoptosis, likely by altering the JAK/ STAT pathway and SIRT1 expression (Fig. 8, Ref. 24). Text in PDF www.elis.sk.

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“…myocardium; ischemia-reperfusion injury; Janus-activated kinase/signal transducer and activator of transcription signaling THE ADIPOCYTOKINE LEPTIN has been shown to protect against ischemia-reperfusion (I/R) injury in various tissues including kidney (9), gut (6), and brain (34). Recently, we reported that leptin, administered at reperfusion, also protects the myocardium against I/R-induced damage (24).…”

mentioning

confidence: 99%

Leptin-induced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore

Smith

Dixon

Wynne

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

100

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Smith CC, Dixon RA, Wynne AM, Theodorou L, Ong SG, Subrayan S, Davidson SM, Hausenloy DJ, Yellon DM. Leptininduced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore. Am J Physiol Heart Circ Physiol 299: H1265-H1270, 2010. First published July 23, 2010; doi:10.1152/ajpheart.00092.2010.-Leptin-induced protection against myocardial ischemia-reperfusion (I/R) injury involves the activation of the reperfusion injury salvage kinase pathway, incorporating phosphatidylinositol 3-kinase-Akt/protein kinase B and p44/42 MAPK, and the inhibition of the mitochondrial permeability transition pore (MPTP). Recently published data indicate that the JAK/STAT signaling pathway, which mediates the metabolic actions of leptin, also plays a pivotal role in cardioprotection. Consequently, in the present study we considered the possibility that JAK/STAT signaling linked to the MPTP may be involved in modulating the cardioprotective actions of leptin. Employing rat in vitro models (Langendorffperfused hearts and cardiomyocytes) of I/R injury, we investigated the actions of leptin (10 nM), administered at reperfusion, in the presence or absence of the JAK2 inhibitor, AG-490 (5 M). Leptin reduced infarct size significantly (control, 60.05 Ϯ 7.41% vs. leptin treated, 29.9 Ϯ 3.24%, P Ͻ 0.05), protection being abolished by AG-490. Time course studies revealed that leptin caused a 171% (P Ͻ 0.001) increase in STAT3/tyrosine-705 phosphorylation at 2.5 min reperfusion; however, increases were not seen at 5, 10, 15, or 30 min reperfusion. Contrasting with STAT3, Akt/serine-473 phosphorylation was not significantly increased until 15 min into the reperfusion phase (140%, P Ͻ 0.05). AG-490 blocked the leptin-induced rise in STAT3 phosphorylation seen at 2.5 min reperfusion but did not influence Akt/serine-473 phosphorylation at 15 min. Leptin reduced the MPTP opening (P Ͻ 0.001), which was blocked by AG-490. This is the first study to yield evidence that JAK/STAT signaling linked to the MPTP plays a role in leptin-induced cardioprotection. Under the experimental conditions employed, STAT3 phosphorylation appears to have occurred earlier during reperfusion than that of Akt. Further research into the interactions between these two signaling pathways in the setting of I/R injury is, however, required. myocardium; ischemia-reperfusion injury; Janus-activated kinase/signal transducer and activator of transcription signaling

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Effect of leptin on renal ischemia-reperfusion damage in rats

Cited by 33 publications

References 31 publications

Leptin Signaling and Obesity

Leptin Signaling and Obesity

The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene expression in the renal tissue of ischemia/reperfusion induced rats

Leptin-induced cardioprotection involves JAK/STAT signaling that may be linked to the mitochondrial permeability transition pore

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