scholarly journals Metabolic Syndrome: the Influence of Adipokines on the L-Arginine-NO Synthase-Nitric Oxide Signaling Pathway

2021 ◽  
Vol 6 (2) ◽  
pp. 22-40
Author(s):  
L. A. Kuznetsova
Keyword(s):  
Metabolic Syndrome ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Posttranslational Modifications ◽  
Maximum Activity ◽  
No Synthase ◽  
Akt Kinase ◽  
Nitric Oxide Signaling ◽  
Endothelial No Synthase ◽  
No Signaling

Metabolic syndrome includes the following symptoms: obesity, hyperlipidemia, hypertension, insulin resistance, and cardiovascular disease. The purpose of this review is to elucidate the role of adipokines in the regulation of the L-arginine-NO-synthas-NO signaling pathway in the pathogenesis of metabolic syndrome. The main questions raised in the review are: how adipokine secretion changes, how the level of their receptors is regulated, and which signaling pathways are involved in the transmission of adipokine signals when coupled to the L-arginine-NO-synthase-NO signaling cascade. Adipokines are peptide hormones that transmit a signal from adipose tissue to targets in the brain, blood vessels, liver, pancreas, muscles, and other tissues. Some adipokines have anti-inflammatory and insulin-sensitive effects: adiponectin, omentin, adipolin, chemerin, progranulin. Others have the negative inflammatory effect in the development ofmetabolic syndrome: visfatin, vaspin, apelin. Adipokines primarily regulate the expression and activity of endothelial NO-synthase. They either activate an enzyme involving 5-AMP protein kinase or Akt kinase, increasing its activity and synthesis of NO in the tissues of healthy patients: adiponectin, adipolin, omentin, or inhibit the activity of eNOS, which leads to a decrease in NO-synthase and suppression of mRNA bioavailability: vaspin, visfatin, apelin in metabolic syndrome, and a decrease in its activity leads to dissociation and endothelial dysfunction. It should be noted that the bioavailability of NO formed by NO-synthase is affected at many levels, including: the expression ofNO-synthase mRNA and its protein; the concentration of L-arginine; the level of cofactors of the reaction; and to detect the maximum activity of endothelial NO-synthase, dimerization of the enzyme is required, posttranslational modifications are important, in particular, phosphorylation of endothelial NO-synthase by serine 1177 with the participation of 5-AMP protein kinase, Akt kinase and other kinases. It should be noted that the participation of adiponectin, omentin, and kemerin in the regulation of the L-arginine-NO-synthase-NO cascade in metabolic syndrom opens up certain opportunities for the development of new approaches for the correction of disorders observed in this disease. The review analyzes the results of research searching in PubMed databases, starting from 2001 and up to 2020 using keywords and adipokine names, more than half of the references of the last 5 years. 

scholarly journals AMP-Activated Protein Kinase Is Involved in Endothelial NO Synthase Activation in Response to Shear Stress

2006 ◽  
Vol 26 (6) ◽  
pp. 1281-1287 ◽  
Author(s):  
Yingjia Zhang ◽  
Tzong-Shyuan Lee ◽  
Erik M. Kolb ◽  
Kai Sun ◽  
Xiao Lu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Protein Kinase ◽  
No Synthase ◽  
Endothelial No Synthase ◽  
Amp Activated Protein Kinase

Association of Glu298Asp Polymorphism of Endothelial NO Synthase Gene with Metabolic Syndrome Development: a Pilot Study

2017 ◽  
Vol 162 (5) ◽  
pp. 615-618
Author(s):  
N. S. Fattakhov ◽  
D. A. Skuratovskaya ◽  
M. A. Vasilenko ◽  
E. V. Kirienkova ◽  
P. A. Zatolokin ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Pilot Study ◽  
No Synthase ◽  
Endothelial No Synthase ◽  
Glu298asp Polymorphism

scholarly journals AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis

2018 ◽  
Vol 116 (1) ◽  
pp. 217-226 ◽  
Author(s):  
Isabel Cordero-Herrera ◽  
Mikael Kozyra ◽  
Zhengbing Zhuge ◽  
Sarah McCann Haworth ◽  
Chiara Moretti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Protein Kinase ◽  
Nadph Oxidase ◽  
Liver Steatosis ◽  
Metabolic Effects ◽  
Dietary Nitrate ◽  
No Signaling ◽  
Nitrate And Nitrite ◽  
Amp Activated Protein Kinase

Advanced age and unhealthy dietary habits contribute to the increasing incidence of obesity and type 2 diabetes. These metabolic disorders, which are often accompanied by oxidative stress and compromised nitric oxide (NO) signaling, increase the risk of adverse cardiovascular complications and development of fatty liver disease. Here, we investigated the therapeutic effects of dietary nitrate, which is found in high levels in green leafy vegetables, on liver steatosis associated with metabolic syndrome. Dietary nitrate fuels a nitrate–nitrite–NO signaling pathway, which prevented many features of metabolic syndrome and liver steatosis that developed in mice fed a high-fat diet, with or without combination with an inhibitor of NOS (l-NAME). These favorable effects of nitrate were absent in germ-free mice, demonstrating the central importance of host microbiota in bioactivation of nitrate. In a human liver cell line (HepG2) and in a validated hepatic 3D model with primary human hepatocyte spheroids, nitrite treatment reduced the degree of metabolically induced steatosis (i.e., high glucose, insulin, and free fatty acids), as well as drug-induced steatosis (i.e., amiodarone). Mechanistically, the salutary metabolic effects of nitrate and nitrite can be ascribed to nitrite-derived formation of NO species and activation of soluble guanylyl cyclase, where xanthine oxidoreductase is proposed to mediate the reduction of nitrite. Boosting this nitrate–nitrite–NO pathway results in attenuation of NADPH oxidase-derived oxidative stress and stimulation of AMP-activated protein kinase and downstream signaling pathways regulating lipogenesis, fatty acid oxidation, and glucose homeostasis. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against liver steatosis associated with metabolic dysfunction.

scholarly journals Protein kinase B/Akt activates c-Jun NH2-terminal kinase by increasing NO production in response to shear stress

2001 ◽  
Vol 91 (4) ◽  
pp. 1574-1581 ◽  
Author(s):  
Young-Mi Go ◽  
Yong Chool Boo ◽  
Heonyong Park ◽  
Matthew C. Maland ◽  
Rakesh Patel ◽  
...  
Keyword(s):  
Shear Stress ◽  
Protein Kinase ◽  
Transient Expression ◽  
Protein Kinase B ◽  
No Synthase ◽  
No Production ◽  
Endothelial No Synthase ◽  
Jnk Activation ◽  
Adenoviral Construct ◽  
Stimulation Of

Laminar shear stress activates c-Jun NH2-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (AktAA) and a constitutively active mutant (AktMyr) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of AktAA in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of AktMyr by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O[Formula: see text], which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.

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