Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPAR. activation in high fructose diet-induced metabolic syndrome

Cannizzaro, Luca, Rossoni, Giuseppe, Savi, Federica, Altomare, Alessandra, Marinello, Cristina, Saethang, Thammakorn, Carini, Marina, Payne, D Michael, Pisitkun, Trairak ORCID: 0000-0001-6677-2271, Aldini, Giancarlo
et al (show 1 more authors) (2017) Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPAR. activation in high fructose diet-induced metabolic syndrome. NUTRITION & METABOLISM, 14 (1). 5-.

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<h4>Background</h4>The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ).<h4>Methods</h4>Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half.<h4>Results</h4>Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented.<h4>Conclusions</h4>Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by PPARγ modulation.

Item Type: Article
Uncontrolled Keywords: AGE-RAGE-oxidative stress axis, Fructose, HNE, Metabolic syndrome, PPAR gamma, Rosiglitazone
Depositing User: Symplectic Admin
Date Deposited: 21 Feb 2020 08:55
Last Modified: 19 Jan 2023 00:01
DOI: 10.1186/s12986-016-0149-z
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