RGD Reference Report - Reversal of the deleterious effects of chronic dietary HFCS-55 intake by PPAR-delta agonism correlates with impaired NLRP3 inflammasome activation. - Rat Genome Database

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Reversal of the deleterious effects of chronic dietary HFCS-55 intake by PPAR-delta agonism correlates with impaired NLRP3 inflammasome activation.

Authors: Collino, M  Benetti, E  Rogazzo, M  Mastrocola, R  Yaqoob, MM  Aragno, M  Thiemermann, C  Fantozzi, R 
Citation: Collino M, etal., Biochem Pharmacol. 2012 Oct 24. pii: S0006-2952(12)00690-9. doi: 10.1016/j.bcp.2012.10.014.
RGD ID: 7175089
Pubmed: PMID:23103566   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bcp.2012.10.014   (Journal Full-text)

Although high-fructose corn syrup (HFCS-55) is the major sweetener in foods and soft-drinks, its potential role in the pathophysiology of diabetes and obesity ("diabesity") remains unclear. Peroxisome-proliferator activated receptor (PPAR)-delta agonists have never been tested in models of sugar-induced metabolic abnormalities. This study was designed to evaluate (i) the metabolic and renal consequences of HFCS-55 administration (15%wt/vol in drinking water) for 30 weeks on male C57Bl6/J mice and (ii) the effects of the selective PPAR-delta agonist GW0742 (1mg/kg/day for 16 weeks) in this condition. HFCS-55 caused (i) hyperlipidemia, (ii) insulin resistance, and (iii) renal injury/inflammation. In the liver, HFCS-55 enhanced the expression of fructokinase resulting in hyperuricemia and caused abnormalities in known insulin-driven signaling events. In the kidney, HFCS-55 enhanced the expression of the NLRP3 (nucleotide-binding domain and leucine-rich-repeat-protein 3) inflammasome complex, resulting in caspase-1 activation and interleukin-1beta production. All of the above effects of HFCS-55 were attenuated by the specific PPAR-delta agonist GW0742. Thus, we demonstrate for the first time that the specific PPAR-delta agonist GW0742 attenuates the metabolic abnormalities and the renal dysfunction/inflammation caused by chronic HFCS-55 exposure by preventing upregulation of fructokinase (liver) and activation of the NLRP3 inflammasome (kidney).

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Albuminuria  ISOIl1b (Mus musculus)7175089; 7175089 RGD 
Albuminuria  IDA 7175089 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1b  (interleukin 1 beta)

Genes (Mus musculus)
Il1b  (interleukin 1 beta)

Genes (Homo sapiens)
IL1B  (interleukin 1 beta)


Additional Information