Russell 2020 Nutrients
|Russell JS, Griffith TA, Naghipour S, Vider J, Du Toit EF, Patel HH, Peart JN, Headrick JP (2020) Dietary α-linolenic acid counters cardioprotective dysfunction in diabetic mice: unconventional PUFA protection. Nutrients 12:E2679.|
Abstract: 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.
• Keywords: -Linolenic acid, Cardioprotection, Caveolae, Caveolins, Cavins, Diabetes, Inflammation, Ischemia-reperfusion, Mitochondria, n-3 PUFA. • Bioblast editor: Plangger M • O2k-Network Lab: US CA San Diego Patel HH
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Diabetes Stress:Ischemia-reperfusion Organism: Mouse Tissue;cell: Heart Preparation: Homogenate
Coupling state: LEAK, OXPHOS, ET Pathway: N, S, NS HRR: Oxygraph-2k