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

Maja Bošković; Maja Živković; Goran Koricanac; Snezana Tepavcevic; Manja Zec; Jasmina Debeljak-Martacic; Aleksandra Stanković

doi:10.3389/fphys.2022.942459

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

Front Physiol. 2022 Sep 21:13:942459. doi: 10.3389/fphys.2022.942459. eCollection 2022.

Authors

Maja Bošković¹, Maja Živković¹, Goran Koricanac², Snezana Tepavcevic², Manja Zec³, Jasmina Debeljak-Martacic⁴, Aleksandra Stanković¹

Affiliations

¹ Laboratory for Radiobiology and Molecular Genetics, "VINČA" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
² Laboratory for Molecular Biology and Endocrinology, "VINČA" Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia.
³ School of Nutritional Sciences and Wellness, University of Arizona, Tucson, AZ, United States.
⁴ Centre of Excellence in Nutrition and Metabolism Research, Institute for Medical Research, National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia.

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.

Keywords: NF-κB; fructose-rich diet; heart; omega-3 PUFA; renin-angiotensin system; walnuts.