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

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