Antioksidativni i antiinflamatorni efekti suplementacije orasima (Juglans regia L.) na srce pacova sa metaboličkim sindromom izazvanim ishranom bogatom fruktozom

Abstract

Povećana konzumacija fruktoze kroz industrijsku hranu doprinosi razvojumetaboličkog sindroma (MetS). MetS prati hronična inflamacija niskog intenziteta kojojdoprinosi oksidativni stres i aktivacija renin-angiotenzin sistema (RAS). Orasi su bogatizvor antioksidanasa i polinezasićenih n-3 masnih kiselina koje imajuantiinflamatorne/imunomodulatorne efekte na kardiometaboličko zdravlje, čijamolekularna osnova nije dovoljno poznata.Konzumacija oraha (2,4 g/dan, 6 nedelja) je smanjila sistolni krvni pritisak kodpacova na ishrani bogatoj fruktozom (10% rastvor, 15 nedelja), pokazala je protektivniefekat na antioksidativnu osu SIRT1-FoxO3a-MnSOD/katalaza i antiinflamatornikapacitet srca (smanjenje AA/EPA) i promovisala antiinflamatorni profil masnih kiselinau plazmi (smanjenje AA/EPA i AA/DHA), koji su kompromitovani fruktoznomishranom. Ulogu negativnih regulatora antioksidativne ose, Nox4 i ChREBP, u srcu trebadodatno ispitati jer je nivo Nox4 povećan i nakon fruktozne ishrane i nakonsuplementacije orasima, dok je nivo ChREBP u jedru smanjen nakon fruktozne ishrane inakon konzumacije oraha kod kontrolnih pacova. Fruktozna ishrana je aktivirala signalniput koji reguliše inflamaciju povećanjem nivoa transkripcionog faktora NF-κB i ključnogenzima RAS-a, АСЕ, dok je suplementacija orasima kod pacova na fruktoznoj ishranipovećala nivo ACE2, kardioprotektivne komponente RAS-a. Na proteinski/iRNK nivoRAS receptora, AT1R i AT2R, nije uticao nijedan od dva nutritivna faktora.Ova studija je potvrdila korisne efekte konzumacije oraha na kardiometaboličkistatus i predloţila mehanizme koji su u osnovi njihovih antiinflamatornih iantioksidativnih efekata u srcu, ukazujući na mogućnost razvoja novih, nefarmakološkihpristupa u terapiji kardiometaboličkih bolesti.

Increased fructose intake via industrial food is associated with metabolic syndrome(MetS). MetS is characterized by chronic low-intensity inflammation caused by oxidativestress and activation of the renin-angiotensin system (RAS). Walnuts are a rich source ofantioxidants and polyunsaturated n-3 fatty acids that exert anti-inflammatory/immunomodulatory effects on cardiometabolic health, which molecularbackground is underexplored.Walnut consumption (2.4 g/day, 6 weeks) reduced systolic blood pressure in ratsfed a fructose-rich diet (10% FRD, 15 weeks), showed a protective effect on theantioxidative axis SIRT1-FoxO3a-MnSOD/catalase and anti-inflammatory cardiac capacity(AA/EPA reduction) and promoted the anti-inflammatory profile of plasma fatty acids(AA/EPA and AA/DHA reduction), which were compromised by FRD. The role of theaxis negative regulators, Nox4 and ChREBP, should be further investigated in the heartbecause the Nox4 level was increased by both, FRD and walnut supplementation, whilethe ChREBP nuclear level was reduced in FRD as well as in control rats subjected towalnuts. FRD activated a signaling pathway that regulated inflammation by increasing thelevels of the transcription factor NF-κB and the key RAS enzyme, ACE, while walnutsupplementation in FRD rats increased ACE2 level, a cardioprotective component of theRAS. The protein/mRNA levels of the RAS receptors, AT1R and AT2R, were not affectedby either of the two nutritional factors.This study confirmed the beneficial effects of walnut consumption oncardiometabolic status and proposed the mechanisms underlying their anti-inflammatoryand antioxidative effects in the heart, indicating the possibility for development of novel,non-pharmacological approaches in cardiometabolic disease therapy.