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

Abstract

Increased fructose consumption has been linked with chronic inflammation and metabolic syndrome (MetS). Activation of the renin-angiotensin system (RAS) and NF-κB have been detected in MetS. Walnuts are a rich source of polyunsaturated omega-3 fatty acids (n-3 PUFA) that were suggested to exert anti-inflammatory effects related to cardio-metabolic health. We hypothesized that walnut supplementation has the capacity to revert unfavorable fructose-rich diet (FRD)-induced activation of cardiac RAS and NF-κB in male rats. Due to the lack of similar studies, we investigated the effects of walnut supplementation (6 weeks) on the expression of four RAS molecules (ACE, ACE2, AT1R, and AT2R) and NF-κB in rat heart after FRD (10% w/v, 9 weeks). In addition, we followed the changes in the n-6/n-3 PUFA ratio in the total pool of heart lipids after both treatments to elucidate the walnut effects on fatty acids in the heart. 36 animals (9 per group) participated in the experiment. FRD significantly increased the ACE protein level in the heart (p < 0.001). Walnut supplementation significantly increased the ACE2 protein level in the heart of FRD (p < 0.001). In addition, walnut supplementation showed a significant main effect on the arachidonic acid/eicosapentaenoic acid ratio (p = 0.004). Walnut supplementation significantly reduced this ratio, in comparison with both, the control group (C vs. FW, p < 0.05) and the FRD group (F vs. FW, p < 0.05). However, walnut treatment failed to revert the significant effect of fructose (p < 0.001) on the elevation of NF-κB protein level. Our results suggest a beneficial effect of walnut supplementation on ACE2 protein level and n-6/n-3 PUFA level in the heart of the animal model of MetS. Such results highlight the approach of omega-3-rich walnut supplementation in the stimulation of endogenous production of favorable molecules in the heart which could be an affordable nutritional treatment formaintenance of cardio-metabolic health.

Pharmacological effect of walnuts consumption on metabolic syndrome: a current view

“…14 Another recent study on mixed nuts (30 g/day walnuts, peanuts and pine nuts) in Korean adults with Mets found significant improvement in TC and LDL-C. 19,20 Supplementing 43 g of walnut daily for eight weeks significantly decreases fasting lipid parameters, including non-HDL-C, apo B, TC, LDL-C, VLDL-C, TG, and VLDL-TG in healthy individuals. 4,17 These results suggests that the increased n-3-PUFA evidence that a high n-3-PUFU intake provides cholesterol-lowering effects through several potential mechanisms non-HDL-C reduced by 5.8%, TC: by 3.9%, apo B by 6.2% VLDL-C by 13.2%, TG by 5.4%, VLDL-TG by 4.0%. 18,21 A study done in 2020 showed that consumption of walnut (J. regia) by ninety (90) hyperlipidaemic patients after 56 days resulted in significant decrease in the levels of TC, TG, LDL cholesterol (LDL-C), and increased HDL-C. 22 It has also been proposed that the favorable changes in lipid profile, which follow long-term consumption of nuts such as walnuts, could also account at least in part for the cardio-protective effect of walnut consumption.…”

“…Metabolic syndrome (Mets) is a medical condition that has a combination of a minimum of three of the following parameters-abdominal obesity (waist circumference (WC) larger than 102 cm for men and 88 cm for women), triglyceride levels of 150 mg/dl or higher, or taking fibrate medication, high density lipoprotein cholesterol (HDL-C) of less than 40 mg/dl for men and 50 mg/dl for women; blood pressure of 130/85 mmHg/ higher/ taking antihypertensive drugs and fasting blood sugar (FBS) of 100 mg/dl or higher/ taking anti-diabetic medications. [1][2][3][4] CVD is the leading cause of death worldwide. 5 In addition to the global and national morbidity and mortality burdens of disease, it imposes a substantial economic burden on society.…”

Food-Derived Up-Regulators and Activators of Angiotensin Converting Enzyme 2: A Review

“…In addition to the aforementioned categories of natural compounds, other natural substances, such as palmitic acid, 17β-estradiol, nicotine, and walnut supplementation (a rich source of polyunsaturated omega-3 fatty acids), all demonstrated the potential to upregulate ACE2 expression. A novel gaseous mediator, hydrogen sulfide (H 2 S), which is endogenously produced during cysteine metabolism, could attenuate atherosclerosis through ACE2 activation .…”