NO synthesis from arginine is favored by α-linolenic acid in mice fed a high-fat diet

Abstract

Alterations in NO availability and signaling play a pivotal role at early stages of the metabolic syndrome (MetSynd). We hypothesized that dietary α-linolenic acid (ALA, 18:3 n-3) favors NO availability by modulating amino acid metabolism, with a specific impact on the arginine-NO pathway. Mice were fed a hyperlipidic diet (285 g lipid/kg, 51.1 % energy), rich in either saturated fatty acids (SFA, provided by palm oil, PALM group) or ALA (provided by linseed oil, LIN group). We measured whole-body NO synthesis and systemic arginine hydrolysis with a tracer-based method, plasma concentration of related metabolites, and hepatic mRNA level of related enzymes, and the study was completed by a transcriptomic analysis in the liver. As expected with this model, hyperlipidic diets resulted in increased adiposity and glycemia after 5 weeks. As compared to PALM mice, LIN mice had a higher plasma nitrite and nitrate concentration, a higher whole-body conversion of arginine into NO vs urea, and a similar plasma concentration of asymmetric dimethylarginine (ADMA), despite a higher expression of the liver dimethylargininase-1. In LIN mice, there was a higher expression of genes involved in PPARα signaling, but a little impact on gene expression related to amino acids and arginine metabolism. This effect cannot be directly ascribed to changes in arginase activity in the liver or ADMA metabolism, nor to direct regulation of the related target genes. In conclusion, dietary ALA favors NO synthesis, which could contribute to rescue NO availability when jeopardized by the nutritional conditions in relation with the initiation of the MetSynd.

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolaemia

“…The decrease in BP accompanied by these changes can be attributed to an increase in the level of NO, the strongest endogenous vasodilating agent. The obtained results are consistent with those of experimental studies on mice, where ALA contained in linseed oil increased L-arginine blood levels with minor changes in ADMA [40]. In other studies, conducted in rats, ALA increased NO concentration [23,41].…”

Intestinal Availability and Metabolic Effects of Dietary Camelina Sphingolipids during the Metabolic Syndrome Onset in Mice

“…In the present study, we used our mouse model of the early steps of the MetS to explore the effects of dietary plant SL provided by camelina meal in a hypercaloric diet. 41 As expected from this model, after 5 weeks on a hypercaloric diet rich in saturated FA and sucrose (HC-Con group), mice exhibited (as compared to those on a normocaloric diet, NC-group) an increase in body weight and adiposity (Table 2 and Figure 1), and in fasting glycemia (Table 4). After only 3 weeks, these alterations were already detectable and were accompanied by higher values of insulinemia and HOMA-IR index (Table 3), and of glucose and insulin postprandial AUC (Figure 2).…”

“…Plant SLs have been shown to exert beneficial effects on some risk factors associated with the MetS, such as altered glucose homeostasis, abnormal lipid profile, and low-grade chronic inflammation. In the present study, we used our mouse model of the early steps of the MetS to explore the effects of dietary plant SL provided by camelina meal in a hypercaloric diet . As expected from this model, after 5 weeks on a hypercaloric diet rich in saturated FA and sucrose (HC-Con group), mice exhibited (as compared to those on a normocaloric diet, NC-group) an increase in body weight and adiposity (Table and Figure ), and in fasting glycemia (Table ).…”

The review of alpha‐linolenic acid: Sources, metabolism, and pharmacology

“…The specific mechanisms included the regulation of lipid metabolism‐related genes (PPARα, HMGCR, and SREBPs) and inhibition of the expression of inflammatory factors (IL‐6, TNF, MCP‐1, and VCAM‐1) and the activity of NADPH oxidase (Han et al, 2015; Winnik et al, 2011). In addition, ALA (40.74% of the diet) protected the vascular endothelial function of HFD‐induced rats by promoting the production of constitutive NO (Hermier et al, 2016). Kaplan et al (2018) also found that ALA (200 mg/kg) improved the smooth muscle damage of the rat thoracic aorta caused by smoking by inhibiting the expression of COX‐2 and PLA 2 and increasing the expression of eNOS.…”