The Molecular and Metabolic Influence of Long Term Agmatine Consumption

Nissim, Itzhak; Horyn, Oksana; Daikhin, Yevgeny; Chen, Pan; Li, Changhong; Wehrli, Suzanne; Nissim, Ilana; Yudkoff, Marc

doi:10.1074/jbc.m113.544726

Cited by 44 publications

(56 citation statements)

References 61 publications

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“…The decrease in the mRNA gene expression of mTOR and SREBP-1c could be the reason for these beneficial effects on lipid profile and on insulin sensitivity. Unlike what was reported in Nissim et al (2014) that AGM consumption can increase the mRNA gene expression of PPAR-α in high-fat-diet-fed rats, PPAR-α was not increased in our study. This discrepancy could be attributed to the difference in AGM treatment duration and dose.…”

Section: Discussioncontrasting

confidence: 86%

“…Moreover, AGM has protective effects against dyslipidemia and associated endothelial dysfunction in rabbits (El-Awady and Suddek 2014). AGM affects hepatic metabolism including fatty acid oxidation, gluconeogenesis and glycolysis (Nissim et al 2014). Furthermore, it increases glucose uptake (Su et al 2009;Chang et al 2010) and enhances glucose utilization by increasing glucose transporter-4 (GLUT-4) mRNA expression in skeletal muscle in streptozotocin-induced diabetic rat model (Hwang et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2

Sharawy

El‐Awady

Megahed

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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Insulin resistance is a serious health condition worldwide; however, its exact mechanisms are still unclear. This study investigates agmatine (AGM; an endogenous metabolite of L-arginine) effects on insulin resistance induced by high fructose diet (HFD) in rats and the possible involved mechanisms. Sprague Dawley rats were fed 60% HFD for 12 weeks, and AGM (10 mg/kg/day, orally) was given from week 9 to 12. AGM significantly reduced HFD-induced elevation in fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) index and liver glycogen content from 3.44-, 3.62- and 2.07- to 2.59-, 2.78- and 1.3-fold, respectively, compared to the control group, while it increased HFD-induced reduction in glucose tolerance. Additionally, AGM significantly decreased HFD-induced elevation in serum triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol levels from 3.18-, 2.97- and 4.75- to 1.25-, 1.25- and 1.07-fold, respectively, compared to control group. Conversely, AGM had no significant effect on HFD-induced changes in fasting glucose, glycosylated hemoglobin, insulin tolerance and high density lipoprotein cholesterol. Furthermore, AGM significantly reduced HFD-induced elevation in mRNA expression of glucose transporter type-2 (GLUT-2), mammalian target of rapamycin (mTOR) and sterol regulatory element-binding protein-1c (SREBP-1c) without affecting that of peroxisome proliferator-activated receptor-alpha (PPAR-α) in the liver. Additionally, AGM enhanced ACh-induced aortic relaxation and attenuated liver steatosis induced by HFD. In conclusion, AGM may have a therapeutic potential in insulin resistance through suppressing SREBP-1c, mTOR and GLUT-2 in liver.

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Section: Discussioncontrasting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2

Sharawy

El‐Awady

Megahed

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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“…HPLC analysis was performed as previously described. 16 D-Serine measurements were performed as previously described with minor adaptations. 17 Briefly, samples and standards were derivatized with Marfey’s reagent (Sigma-Aldrich; cat#71478) Na-(2,4-Dinitro-5-fluorophenyl)-l-alaninamide).…”

Section: Methodsmentioning

confidence: 99%

“…Serine isomers were separated with the use of LC-MS technique as in (see Nissim et al . 16 ). Quantification of D-Serine was done with 13C-Serine (Sigma-Aldrich) using an isotope dilution approach.…”

Section: Methodsmentioning

confidence: 99%

Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny

et al. 2017

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Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist D-serine were accompanied by increased expression of the D-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny. Increased Dao1 transcription was associated with enrichment of permissive epigenetic marks on histone proteins in the hippocampus of male cocaine-sired progeny, some of which were enhanced near the Dao1 locus. Finally, hippocampal administration of D-serine reversed both the memory formation and synaptic plasticity deficits. Collectively, these results demonstrate that paternal cocaine exposure produces epigenetic remodeling in the hippocampus leading to NMDA receptor-dependent memory formation and synaptic plasticity impairments only in male progeny, which has significant implications for the male descendants of chronic cocaine users.

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“…Either plasma samples and/or a neutralized perchloric acid (PCA) extract prepared from liver were used for metabolites measurement. The concentration of amino acids was determined by Agilent 1260 HPLC system, using precolumn derivatization with o-phthalaldehyde (Nissim et al 2012;Nissim et al 2014). Organic acids levels were determined by the isotope-dilution approach and GC-MS system (Weinberg et al 2000).…”

Section: Metabolite Measurementsmentioning

confidence: 99%

Collapse of the hepatic gene regulatory network in the absence of FoxA factors

Reizel

Morgan

Gao

et al. 2020

Preprint

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The FoxA transcription factors are critical for liver development through their pioneering activity, which initiates a highly complex regulatory network thought to become progressively resistant to the loss of any individual hepatic transcription factor via mutual redundancy. To investigate the dispensability of FoxA factors for maintaining this regulatory network, we ablated all FoxA genes in the adult mouse liver. Remarkably, loss of FoxA caused rapid hepatocyte dedifferentiation manifested by a massive reduction in the expression of key liver genes. Interestingly, expression of these genes was reduced back to the low levels of the fetal prehepatic endoderm stage, leading to necrosis and lethality within days. Mechanistically, we found FoxA proteins to be required for maintaining enhancer activity, chromatin accessibility, nucleosome positioning and binding by HNF4a. Thus, the FoxA factors act continuously, guarding hepatic enhancer activity throughout life.

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The Molecular and Metabolic Influence of Long Term Agmatine Consumption

Cited by 44 publications

References 61 publications

Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2

Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2

Paternal cocaine taking elicits epigenetic remodeling and memory deficits in male progeny

Collapse of the hepatic gene regulatory network in the absence of FoxA factors

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