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 razvoju metaboličkog sindroma (MetS). MetS prati hronična inflamacija niskog intenziteta kojoj doprinosi oksidativni stres i aktivacija renin-angiotenzin sistema (RAS). Orasi su bogat izvor antioksidanasa i polinezasićenih n-3 masnih kiselina koje imaju antiinflamatorne/imunomodulatorne efekte na kardiometaboličko zdravlje, čija molekularna osnova nije dovoljno poznata. Konzumacija oraha (2,4 g/dan, 6 nedelja) je smanjila sistolni krvni pritisak kod pacova na ishrani bogatoj fruktozom (10% rastvor, 15 nedelja), pokazala je protektivni efekat na antioksidativnu osu SIRT1-FoxO3a-MnSOD/katalaza i antiinflamatorni kapacitet srca (smanjenje AA/EPA) i promovisala antiinflamatorni profil masnih kiselina u plazmi (smanjenje AA/EPA i AA/DHA), koji su kompromitovani fruktoznom ishranom. Ulogu negativnih regulatora antioksidativne ose, Nox4 i ChREBP, u srcu treba dodatno ispitati jer je nivo Nox4 povećan i nakon fruktozne ishrane i nakon suplementacije orasima, dok je nivo ChREBP u jedru smanjen nakon fruktozne ishrane i nakon konzumacije oraha kod kontrolnih pacova. Fruktozna ishrana je aktivirala signalni put koji reguliše inflamaciju povećanjem nivoa transkripcionog faktora NF-κB i ključnog enzima RAS-a, АСЕ, dok je suplementacija orasima kod pacova na fruktoznoj ishrani povećala nivo ACE2, kardioprotektivne komponente RAS-a. Na proteinski/iRNK nivo RAS receptora, AT1R i AT2R, nije uticao nijedan od dva nutritivna faktora. Ova studija je potvrdila korisne efekte konzumacije oraha na kardiometabolički status i predloţila mehanizme koji su u osnovi njihovih antiinflamatornih i antioksidativnih efekata u srcu, ukazujući na mogućnost razvoja novih, nefarmakoloških pristupa 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 oxidative stress and activation of the renin-angiotensin system (RAS). Walnuts are a rich source of antioxidants and polyunsaturated n-3 fatty acids that exert anti- inflammatory/immunomodulatory effects on cardiometabolic health, which molecular background is underexplored. Walnut consumption (2.4 g/day, 6 weeks) reduced systolic blood pressure in rats fed a fructose-rich diet (10% FRD, 15 weeks), showed a protective effect on the antioxidative 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 the axis negative regulators, Nox4 and ChREBP, should be further investigated in the heart because the Nox4 level was increased by both, FRD and walnut supplementation, while the ChREBP nuclear level was reduced in FRD as well as in control rats subjected to walnuts. FRD activated a signaling pathway that regulated inflammation by increasing the levels of the transcription factor NF-κB and the key RAS enzyme, ACE, while walnut supplementation in FRD rats increased ACE2 level, a cardioprotective component of the RAS. The protein/mRNA levels of the RAS receptors, AT1R and AT2R, were not affected by either of the two nutritional factors. This study confirmed the beneficial effects of walnut consumption on cardiometabolic status and proposed the mechanisms underlying their anti-inflammatory and antioxidative effects in the heart, indicating the possibility for development of novel, non-pharmacological approaches in cardiometabolic disease therapy.