{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:00:15Z","timestamp":1772172015999,"version":"3.50.1"},"reference-count":143,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001791","name":"Griffith University","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001791","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Whether dietary omega-3 (n-3) polyunsaturated fatty acid (PUFA) confers cardiac benefit in cardiometabolic disorders is unclear. We test whether dietary \u03b1-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\u03b2 (GSK3\u03b2); 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-GSK3\u03b2, 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 \u201cun-conventional\u201d protection remains to be identified.<\/jats:p>","DOI":"10.3390\/nu12092679","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T09:29:28Z","timestamp":1599038968000},"page":"2679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Dietary \u03b1-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-9955","authenticated-orcid":false,"given":"Jake","family":"Russell","sequence":"first","affiliation":[{"name":"School of Medical Science, Griffith University Gold Coast, Southport QLD 4217, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tia","family":"Griffith","sequence":"additional","affiliation":[{"name":"School of Medical Science, Griffith University Gold Coast, Southport QLD 4217, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6624-5674","authenticated-orcid":false,"given":"Saba","family":"Naghipour","sequence":"additional","affiliation":[{"name":"School of Medical Science, Griffith University Gold Coast, Southport QLD 4217, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Vider","sequence":"additional","affiliation":[{"name":"School of Medical Science, Griffith University Gold Coast, Southport QLD 4217, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Du Toit","sequence":"additional","affiliation":[{"name":"School of Medical Science, Griffith University Gold Coast, Southport QLD 4217, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6722-9625","authenticated-orcid":false,"given":"Hemal","family":"Patel","sequence":"additional","affiliation":[{"name":"VA San Diego Healthcare System and Department of Anesthesiology, University of California, San Diego, CA 92093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Peart","sequence":"additional","affiliation":[{"name":"School of Medical Science, Griffith University Gold Coast, Southport QLD 4217, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Headrick","sequence":"additional","affiliation":[{"name":"School of Medical Science, Griffith University Gold Coast, Southport QLD 4217, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1016\/j.jacc.2011.06.063","article-title":"Omega-3 fatty acids and cardiovascular disease: Effects on risk factors, molecular pathways, and clinical events","volume":"58","author":"Mozaffarian","year":"2011","journal-title":"J. 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