Anti‑Inflammatory and Hepatoprotective Roles of Oleic and Linoleic Acids in a Wistar Rat Model of Type 2 Diabetes

Background The global rise in type 2 diabetes mellitus (T2DM) poses a major healthcare challenge, driven by chronic inflammation, oxidative stress, and hepatic dysfunction. Conventional therapies primarily target glycemic control but often fail to address tissue-level injury. Dietary fatty acids such as oleic acid (OA) and linoleic acid (LA) may offer adjunctive therapeutic benefits. Methods Eighty male Wistar rats (150–180g) were induced with T2DM using 10% fructose supplementation for six weeks followed by a single intraperitoneal injection of streptozotocin (35 mg/kg). Animals with fasting blood glucose > 250 mg/dL were randomized into eight groups (n = 10): normal control, non-diabetic + OA, non-diabetic + LA, diabetic control, diabetic + OA, diabetic + LA, diabetic + OA + LA, and diabetic + metformin. Treatments lasted six weeks. Plasma and pancreatic cytokines, oxidative stress markers, hepatic injury enzymes, and histological changes in liver and pancreas were assessed. Results Compared with diabetic controls, OA and LA significantly reduced pro-inflammatory cytokines (TNF-α, IL-6), increased anti-inflammatory IL-10, lowered malondialdehyde levels, and enhanced antioxidant enzyme activities (CAT, SOD) (p < 0.0001). Hepatic injury markers were normalized, and histological analysis revealed improved hepatic and pancreatic architecture. Combined OA + LA treatment produced synergistic benefits, including enhanced PDX-1 expression and greater histological restoration, though effects varied across parameters. Overall, OA and LA demonstrated efficacy comparable to metformin. Conclusion Oleic and linoleic acids exert anti-inflammatory, antioxidant, and hepatoprotective effects in a rat model of T2DM. Their combined administration showed synergistic benefits, underscoring the translational potential of dietary fatty acid modulation as an adjunctive strategy for managing T2DM-associated complications.