Walnut Supplementation Restores the SIRT1‐FoxO3a‐MnSOD/Catalase Axis in the Heart, Promotes an Anti‐Inflammatory Fatty Acid Profile in Plasma, and Lowers Blood Pressure on Fructose‐Rich Diet

Abstract

The benefits of walnut (Juglans regia) consumption for metabolic health are known, but the molecular background underlying their putative antioxidant and anti-inflammatory/immunomodulatory effects is underexplored. We assessed that walnut supplementation (6 weeks) reverted unfavorable changes of the SIRT1/FoxO3a/MnSOD/catalase axis in the heart induced by fructose-rich diet (FRD). Intriguingly, Nox4 was increased by both FRD and walnut supplementation. FRD increased the cytosolic fraction and decreased the nuclear fraction of the uniquely elucidated ChREBP in the heart. The ChREBP nuclear fraction was decreased in control rats subjected to walnuts. In addition, walnut consumption was associated with a reduction in systolic BP in FRD and a decrease in fatty acid AA/EPA and AA/DHA ratios in plasma. In summary, the protective effect of walnut supplementation was detected in male rats following the fructose-induced decrease in antioxidative/anti-inflammatory capacity of cardiac tissue and increase in plasma predictors of low-grade inflammation. The current results provide a novel insight into the relationship between nutrients, cellular energy homeostasis, and the modulators of inflammatory/immune response in metabolic syndrome, emphasizing the heart and highlighting a track for translation into nutrition and dietary therapeutic approaches against metabolic disease.

Walnut supplementation after fructose-rich diet is associated with a beneficial fatty acid ratio and increased ACE2 expression in the rat heart

“…Totest our hypothesis, we investigated the RAS-mediated inflammatory effects of FRD (10% w/v, 9 weeks) and antiinflammatory effects of walnut supplementation (6 weeks) based on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart. Based on the relationship between the n-6/n-3 ratio and inflammation supported by our previous findings in plasma (Bošković et al, 2021) regarding fructose and walnut supplementation effects on AA/EPA and AA/docosahexaenoic acid (DHA, 22: 6n-3), we hypothesized that walnut-enriched diet should also have the capacity to restore beneficial ratios of these PUFAs in the heart.…”

“…In the current study, we demonstrated a decrease in the AA/EPA ratio in the heart after walnut consumption. Recently, we also reported a walnut-associated decrease of plasma AA/EPA ratio in the same animal model of MetS (Bošković et al, 2021). The impact of PUFA supplementation on ACE2 levels in the MetS has not been investigated, yet.…”

“…frontiersin.org molecular level by walnut supplementation (Zec et al, 2020;Bošković et al, 2021;Stanišić et al, 2021). The main novelty in the current study is a significant main effect of walnut supplementation on the ACE2 protein level in the heart, which is in line with previously published significant reduction of systolic blood pressure in the current animal model of MetS (Bošković et al, 2021).…”

“…frontiersin.org molecular level by walnut supplementation (Zec et al, 2020;Bošković et al, 2021;Stanišić et al, 2021). The main novelty in the current study is a significant main effect of walnut supplementation on the ACE2 protein level in the heart, which is in line with previously published significant reduction of systolic blood pressure in the current animal model of MetS (Bošković et al, 2021). ACE2 deficiency was associated with modest systolic hypertension (Gurley et al, 2006) Frontiers in Physiology frontiersin.org and ACE2 activators lowered blood pressure (Hernandez Prada et al, 2008) and improved cardiac function (Dong et al, 2012;Murca et al, 2012).…”

Oxypaeoniflorin Prevents Acute Lung Injury Induced by Lipopolysaccharide through the PTEN/AKT Pathway in a Sirt1‐Dependent Manner

“…Silencing information regulator 2-related enzyme 1 (Sirt1) is a deacetylase at the consumption of NAD + , which is associated with cell cycle, gene silencing, glucose and fat metabolism, oxidative stress, and aging [ 5 ]. Recent studies have unveiled that Sirt1 activation exerted protection in ALI by blocking oxidative stress, inflammation, and apoptosis of pulmonary epithelial cells while Sirt1 knockout can aggravate ALI by activating inflammatory response [ 6 – 8 ].…”