α‐Linolenic acid and exercise training independently, and additively, decrease blood pressure and prevent diastolic dysfunction in obese Zucker rats

Abstract

Although α-linolenic acid (ALA) and endurance exercise training independently attenuate hyperlipidaemia-related cardiovascular derangements, there is a paucity of information pertaining to their mechanisms of action and efficacy when combined as a preventative therapeutic approach. Therefore, we used obese Zucker rats to investigate the independent and combined effects of these interventions on cardiovascular disease. Specifically, animals were randomly assigned to one of the following groups: control diet-sedentary, ALA supplemented-sedentary, control diet-exercise trained or ALA supplemented-exercise trained. Following a 4 week intervention, although the independent and combined effects of ALA and exercise reduced (P < 0.05) the serum free/esterified cholesterol ratio, only the ALA supplemented-exercise trained animals displayed a reduction in the content of both serum free and esterified cholesterol. Moreover, although ALA and endurance training individually increased cardiac output, stroke volume and end-diastolic volume, as well as reduced left ventricle fibrosis, mean blood pressure and total peripheral resistance, these responses were all greater following the combined intervention (ALA supplemented-exercise trained). These effects occurred independent of changes in oxidative phosphorylation proteins, markers of oxidative stress or endogenous anti-oxidant capacity. We propose that the beneficial effects of a combined intervention occur as a result of divergent mechanisms of action elicited by ALA and endurance exercise because only exercise training increased the capillary content in the left ventricle and skeletal muscle, and tended to decrease protein carbonylation in the left ventricle (P = 0.06). Taken together, our data indicate that combining ALA and endurance exercise provides additional improvements in cardiovascular disease risk reduction compared to singular interventions in the obese Zucker rat.

α-linolenic acid supplementation prevents exercise-induced improvements in white adipose tissue mitochondrial bioenergetics and whole-body glucose homeostasis in obese Zucker rats

“…Whole-body glucose tolerance and body mass in response to ALA and exercise We have previously reported in these same animals that ALA supplementation appropriately increased the ALA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) contents of lipids within the blood and the liver, verifying the dietary intervention [41]. In the present study, we report that the consumption of ALA independently did not alter body weight throughout the experimental protocol (Fig.…”

“…While the importance of adipose tissue for glucose homeostasis is well understood [2], it is unlikely that eWAT alone accounted for these findings in the ALA-Ex group as glucose tolerance was not different between ALA-Sed and CON-Sed animals despite a decrease in insulin signalling in the ALA-Sed animals. Indeed, recent work published from our lab found that insulin sensitivity in the liver was lower in the ALA-Ex compared with the CON-Ex group [41], and thus it is possible that the ability of insulin to suppress hepatic glucose output was also attenuated in the ALA-Ex group, which would explain the profound impact of the combined intervention on glucose tolerance in spite of increased skeletal muscle insulin sensitivity. Therefore, taken together, we provide clear evidence that ALA prevents exercised-induced improvements in wholebody glucose homeostasis in an obese rodent model, an effect that appears to involve, at least in part, alterations within eWAT.…”

“…Body weight was measured every week, while glucose tolerance tests were performed 48 h before animals were anaesthetised with isoflurane (4% in O 2 ) to conduct experiments described below. We have previously reported on the effects of these interventions with respect to cardiovascular function and hepatic lipid content [40,41]. Experimenters were not blind to group assignment during the conduction of experiments and all experiments were conducted in accordance with protocols approved by the University of Guelph Animal Care Committee.…”

α-Linolenic acid but not linolenic acid protects against hypertension: critical role of SIRT3 and autophagic flux

“…Four-week-old male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar-Kyoto (WKY) control rats were purchased from Vital River Laboratory (Beijing, China). The control diet (no.AIN-93G; 20% protein, 64% carbohydrate and 16% fat), LA-supplemented diet (no.AIN-93G + 10% safflower oil; 20% protein, 54% carbohydrate, and 26% fat) and ALA-supplemented diet (no.AIN-93G + 10% flaxseed oil; 20% protein, 54% carbohydrate and 26% fat;), as reported previously 13,14 , were obtained from Research Diets (New Brunswick, NJ). The animals were randomly divided into four groups with different diets for 8 weeks using a completely randomized design: (1) WKY: the normotensive WKYs fed with the control diet; (2) SHR: the SHRs fed with the control diet; (3) SHR + LA: the SHRs fed with LA-supplemented diet; (4) SHR + ALA: the SHRs fed with ALA-supplemented diet.…”

Ablating the Rab‐GTPase activating protein TBC1D1 predisposes rats to high‐fat diet‐induced cardiomyopathy

“…Protein carbonylation was assessed in left ventricle crude homogenates using the commercially available OxyBlot Oxidized Protein Detection Kit (catalogue no. S7150; Millipore, Billerica, MA, USA), as described previously (Barbeau et al 2017).…”