Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection
Whether dietary omega-3 (n-3) polyunsaturated fatty acid (PUFA) confers cardiac benefit in cardiometabolic disorders is unclear. We test whether dietary -linolenic acid (ALA) enhances myocardial resistance to ischemia-reperfusion (I-R) and responses to ischemic preconditioning (IPC) in type 2 diabet...
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doaj-647b4ccb80ec43ba85e047bef2e2d4522020-11-25T03:19:38ZengMDPI AGNutrients2072-66432020-09-01122679267910.3390/nu12092679Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA ProtectionJake S. Russell0Tia A. Griffith1Saba Naghipour2Jelena Vider3Eugene F. Du Toit4Hemal H. Patel5Jason N. Peart6John P. Headrick7School of Medical Science, Griffith University Gold Coast, Southport, QLD 4217, AustraliaSchool of Medical Science, Griffith University Gold Coast, Southport, QLD 4217, AustraliaSchool of Medical Science, Griffith University Gold Coast, Southport, QLD 4217, AustraliaSchool of Medical Science, Griffith University Gold Coast, Southport, QLD 4217, AustraliaSchool of Medical Science, Griffith University Gold Coast, Southport, QLD 4217, AustraliaVA San Diego Healthcare System and Department of Anesthesiology, University of California, San Diego, CA 92093, USASchool of Medical Science, Griffith University Gold Coast, Southport, QLD 4217, AustraliaSchool of Medical Science, Griffith University Gold Coast, Southport, QLD 4217, AustraliaWhether dietary omega-3 (n-3) polyunsaturated fatty acid (PUFA) confers cardiac benefit in cardiometabolic disorders is unclear. We test whether dietary -linolenic acid (ALA) enhances myocardial resistance to ischemia-reperfusion (I-R) and responses to ischemic preconditioning (IPC) in type 2 diabetes (T2D); and involvement of conventional PUFA-dependent mechanisms (caveolins/cavins, kinase signaling, mitochondrial function, and inflammation). Eight-week male C57Bl/6 mice received streptozotocin (75 mg/kg) and 21 weeks high-fat/high-carbohydrate feeding. Half received ALA over six weeks. Responses to I-R/IPC were assessed in perfused hearts. Localization and expression of caveolins/cavins, protein kinase B (AKT), and glycogen synthase kinase-3 β (GSK3β); mitochondrial function; and inflammatory mediators were assessed. ALA reduced circulating leptin, without affecting body weight, glycemic dysfunction, or cholesterol. While I-R tolerance was unaltered, paradoxical injury with IPC was reversed to cardioprotection with ALA. However, post-ischemic apoptosis (nucleosome content) appeared unchanged. Benefit was not associated with shifts in localization or expression of caveolins/cavins, p-AKT, p-GSK3β, or mitochondrial function. Despite mixed inflammatory mediator changes, tumor necrosis factor-a (TNF-a) was markedly reduced. Data collectively reveal a novel impact of ALA on cardioprotective dysfunction in T2D mice, unrelated to caveolins/cavins, mitochondrial, or stress kinase modulation. Although evidence suggests inflammatory involvement, the basis of this “un-conventional” protection remains to be identified.https://www.mdpi.com/2072-6643/12/9/2679-linolenic acidn-3 PUFAdiabetescardioprotectioncaveolaecaveolins |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jake S. Russell Tia A. Griffith Saba Naghipour Jelena Vider Eugene F. Du Toit Hemal H. Patel Jason N. Peart John P. Headrick |
spellingShingle |
Jake S. Russell Tia A. Griffith Saba Naghipour Jelena Vider Eugene F. Du Toit Hemal H. Patel Jason N. Peart John P. Headrick Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection Nutrients -linolenic acid n-3 PUFA diabetes cardioprotection caveolae caveolins |
author_facet |
Jake S. Russell Tia A. Griffith Saba Naghipour Jelena Vider Eugene F. Du Toit Hemal H. Patel Jason N. Peart John P. Headrick |
author_sort |
Jake S. Russell |
title |
Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection |
title_short |
Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection |
title_full |
Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection |
title_fullStr |
Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection |
title_full_unstemmed |
Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection |
title_sort |
dietary α-linolenic acid counters cardioprotective dysfunction in diabetic mice: unconventional pufa protection |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2020-09-01 |
description |
Whether dietary omega-3 (n-3) polyunsaturated fatty acid (PUFA) confers cardiac benefit in cardiometabolic disorders is unclear. We test whether dietary -linolenic acid (ALA) enhances myocardial resistance to ischemia-reperfusion (I-R) and responses to ischemic preconditioning (IPC) in type 2 diabetes (T2D); and involvement of conventional PUFA-dependent mechanisms (caveolins/cavins, kinase signaling, mitochondrial function, and inflammation). Eight-week male C57Bl/6 mice received streptozotocin (75 mg/kg) and 21 weeks high-fat/high-carbohydrate feeding. Half received ALA over six weeks. Responses to I-R/IPC were assessed in perfused hearts. Localization and expression of caveolins/cavins, protein kinase B (AKT), and glycogen synthase kinase-3 β (GSK3β); mitochondrial function; and inflammatory mediators were assessed. ALA reduced circulating leptin, without affecting body weight, glycemic dysfunction, or cholesterol. While I-R tolerance was unaltered, paradoxical injury with IPC was reversed to cardioprotection with ALA. However, post-ischemic apoptosis (nucleosome content) appeared unchanged. Benefit was not associated with shifts in localization or expression of caveolins/cavins, p-AKT, p-GSK3β, or mitochondrial function. Despite mixed inflammatory mediator changes, tumor necrosis factor-a (TNF-a) was markedly reduced. Data collectively reveal a novel impact of ALA on cardioprotective dysfunction in T2D mice, unrelated to caveolins/cavins, mitochondrial, or stress kinase modulation. Although evidence suggests inflammatory involvement, the basis of this “un-conventional” protection remains to be identified. |
topic |
-linolenic acid n-3 PUFA diabetes cardioprotection caveolae caveolins |
url |
https://www.mdpi.com/2072-6643/12/9/2679 |
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