AdipoRon Attenuates Inflammation and Impairment of Cardiac Function Associated With Cardiopulmonary Bypass–Induced Systemic Inflammatory Response Syndrome

Jenke, Alexander; Yazdanyar, Mariam; Miyahara, Shunsuke; Chekhoeva, Agunda; Immohr, Moritz Benjamin; Kistner, Julia; Boeken, Udo; Lichtenberg, Artur; Akhyari, Payam

doi:10.1161/jaha.120.018097

Cited by 18 publications

(17 citation statements)

References 29 publications

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“…Targeting CTRP1 may be used as a therapeutic management to treat cardiac dysfunction post MI [ 84 ]. In the rat model, AdipoRon (an adiponectin receptor) was found to decrease inflammation and weaken heart functions caused by CPB through mediation of AMPK that upregulates immunosuppressive IL-10 and inhibits proinflammatory cytokines like TLR4 and TNF-α in cardiac cells [ 85 ]. Mesenchymal stem cells have been used therapeutically in mice for pressure overload-led heart failure, which involved the existence of plasma adiponectin and T-cadherin expression as well as biogenesis of exosome in the treated mesenchymal stem cells with a high level of exosomes in plasma.…”

Section: Significant Cellular Roles Of Adiponectin As a Rescue Hormon...mentioning

confidence: 99%

Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

Aljafary

Al-Suhaimi

2022

Pharmaceutics

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The adipose tissue, regardless of its role in generating and storing energy, acts as a key player as an endocrine tissue, producing a wide scale of cytokines/hormones called adipokines. Adipokines such as leptin, resistin, visfatin and osteopontin own pro-inflammatory effects on the cardiovascular system in some cases. In contrast, some adipokines have cardioprotective and anti-inflammatory impacts including adiponectin, omentin, and apelin. One of the key adipokines is adiponectin, the abundant peptide regulating hormone that is released mainly by adipocytes and cardiomyocytes as well as by endothelial and skeletal cells. It acts through two main receptors: AdipoR1 and AdipoR2, forming the “Adiponectin system” which effectively exerts its cellular mechanisms and responses in target cells. It regulates various metabolic processes, while adiponectin is the adipocyte hormone known for its cardioprotective impact in clinical and experimental research. It is also a well-effector metabolic adipokine, since weight loss or diet restriction show a link with rises in adiponectin concentrations, which is accompanied with increasing insulin sensitivity, glucose, and lipids-regulation via adiponectin’s antioxidant, anti-inflammatory, anti-fibrotic actions. The high adiponectin level made it an attractive player in developing therapeutical treatments for metabolic syndromes and cardiovascular disease. The elevated plasma levels of adiponectin are mostly attributed to its benefits on cardio-metabolism. In some cases, adiponectin has been paradoxically accompanied with elevated risk of cardiovascular disease, so higher adiponectin concentration is a marker of poor prediction. Thus, the adiponectin system is attractive to researchers as a biomarker of heart disease advancement and a predictor of prognosis during the term of some cardiovascular diseases and its mechanical functions in Hypertension and diabetic patients. This review highlights the physiological roles of adiponectin as an anti-inflammatory and cardioprotective hormone as well as how it plays as a biomarker and potential therapeutic tool in the cardiovascular system in adult, children, and adolescents. The adiponectin system may be seen as a rescue hormone aiding in remodeling of the cardiovascular system on both cellular and molecular levels. The paradox role of adiponectin relevant to cardiovascular mortality should be taken into consideration.

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Section: Significant Cellular Roles Of Adiponectin As a Rescue Hormon...mentioning

confidence: 99%

Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

Aljafary

Al-Suhaimi

2022

Pharmaceutics

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“…In the liver, AdipoRon attenuated carbon tetrachloride-induced liver damage by inhibiting the expression of proinflammatory cytokines and activation of hepatic stellate cells [ 14 ]. In the heart, AdipoRon relieved cardiopulmonary bypass-induced cardiac inflammation and functional impairment by inhibiting TLR4/TNF- α signaling in cardiomyocytes [ 13 ]. Therefore, these results suggest that AdipoRon alleviates mechanical nociception in SNI mice by inhibiting TNF- α expression in the spinal cord.…”

Section: Discussionmentioning

confidence: 99%

AdipoRon Engages Microglia to Antinociception through the AdipoR1/AMPK Pathway in SNI Mice

Fang

Wang

et al. 2023

Mediators of Inflammation

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Background. Microglia-associated neuroinflammation plays a crucial role in the initiation and development of neuropathic pain (NeuP). AdipoRon is an analog of adiponectin that exerts an anti-inflammatory effect in various diseases through the adiponectin receptor 1 (AdipoR1) signaling mechanism. Adenosine monophosphate-activated protein kinase (AMPK) is a downstream target of AdipoR1, and the AdipoR1/AMPK pathway is involved in the regulation of inflammation. This study is aimed at investigating whether AdipoRon could alleviate NeuP by inhibiting the expression of microglia-derived tumor necrosis factor-alpha (TNF-α) through the AdipoR1/AMPK pathway. Methods. In vivo, the NeuP model was established in mice through the spared nerve injury. The von Frey test was used to detect the effect of AdipoRon on the mechanical paw withdrawal threshold. Western Blot was performed to detect the effects of AdipoRon on the expression of TNF-α, AdipoR1, AMPK, and p-AMPK. Immunofluorescence was performed to observe the effects of AdipoRon on spinal microglia. In vitro, lipopolysaccharide (LPS) was used to induce inflammatory responses in BV2 cells. The effect of AdipoRon on cell proliferation was detected by CCK-8. qPCR was used to examine the effects of AdipoRon on the expression of TNF-α and polarization markers. And the effect of AdipoRon on the AdipoR1/AMPK pathway was confirmed by Western Blot. Results. Intraperitoneal injection of AdipoRon alleviated mechanical nociception in SNI mice, and the application of AdipoRon reduced the expression of TNF-α and the number of microglia in the ipsilateral spinal cord. Additionally, AdipoRon decreased the protein level of AdipoR1 and increased the protein level of p-AMPK in the ipsilateral spinal cord. In vitro, AdipoRon inhibited BV2 cell proliferation and reversed LPS-induced TNF-α expression and polarization imbalance. Furthermore, AdipoRon reversed the LPS-induced increase in AdipoR1 expression and decrease in p-AMPK expression in BV2 cells. Conclusions. AdipoRon may alleviate NeuP by reducing microglia-derived TNF-α through the AdipoR1/AMPK pathway.

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“…Importantly, AdipoRon attenuated postischemic myocardial apoptosis through both AMPK-mediated and AMPK-independent signaling. In another study, Jenke et al [ 36 ] showed that AdipoRon reduces inflammation and impairment of cardiac function associated to systemic inflammatory response syndrome induced by cardiopulmonary bypass (CPB) in rats. Oral gavage of AdipoRon resulted in activation of AMPK and reduction in CPB-upregulation of TNF-α and IL-β as well as NADPH oxidase and inducible nitric oxide synthase (iNOS) [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…In another study, Jenke et al [ 36 ] showed that AdipoRon reduces inflammation and impairment of cardiac function associated to systemic inflammatory response syndrome induced by cardiopulmonary bypass (CPB) in rats. Oral gavage of AdipoRon resulted in activation of AMPK and reduction in CPB-upregulation of TNF-α and IL-β as well as NADPH oxidase and inducible nitric oxide synthase (iNOS) [ 36 ]. Gu et al [ 37 ] demonstrated that AdipoRon protects against contrast-induced nephropathy by suppressing oxidative stress and inflammation by activation of the AMPK pathway.…”

Section: Discussionmentioning

confidence: 99%

AdipoRon, an Orally Active, Synthetic Agonist of AdipoR1 and AdipoR2 Receptors Has Gastroprotective Effect in Experimentally Induced Gastric Ulcers in Mice

et al. 2021

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Introduction: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. Methods: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg /kg p.o) was compared to omeprazole (20 mg/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities; glutathione (GSH) level; and IL-1β, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. Results: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1β expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. Conclusions: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.

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AdipoRon Attenuates Inflammation and Impairment of Cardiac Function Associated With Cardiopulmonary Bypass–Induced Systemic Inflammatory Response Syndrome

Cited by 18 publications

References 29 publications

Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

Adiponectin System (Rescue Hormone): The Missing Link between Metabolic and Cardiovascular Diseases

AdipoRon Engages Microglia to Antinociception through the AdipoR1/AMPK Pathway in SNI Mice

AdipoRon, an Orally Active, Synthetic Agonist of AdipoR1 and AdipoR2 Receptors Has Gastroprotective Effect in Experimentally Induced Gastric Ulcers in Mice

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