Modulation of Brain Antioxidant Defense, Inflammation, and SIRT1 Activity by a Sunflower Oil-Based High-Fat Diet: Protective Role of L-Arginine in Rats

Abstract

BackgroundChronic consumption of omega-6-enriched dietary fat may disturb brain redox balance and neuroinflammatory homeostasis. Among the sirtuins, sirtuin 1 (SIRT1) exerts critical neuroprotective functions by suppressing oxidative stress and inflammatory signaling; however, the impact of sunflower oil-based high-fat diets (SO-HFD) on brain SIRT1 activity has not been investigated.ObjectiveThis study aimed to investigate the effects of SO-HFD on oxidative stress parameters, inflammatory markers, and SIRT1 activity in rat brain tissue, and to evaluate the potential modulatory role of L-arginine supplementation.MethodsFour-week-old female Sprague-Dawley rats were allocated into three groups: control, SO-HFD, and SO-HFD + L-arginine. Both SO-HFD groups were fed a diet containing sunflower oil for 16 weeks; from week 10 onward, 1.5% L-arginine was supplemented in the drinking water of the SO-HFD + L-arginine group. Following the 16-week protocol, serum and brain specimens were collected. Serum biochemical parameters and adiponectin were quantified; brain homogenates were assayed for lipid peroxidation (MDA), reduced glutathione (GSH), protein thiols (protein-SH), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) levels, and SIRT1 activity.ResultsAlthough brain MDA levels were not significantly elevated, SO-HFD animals exhibited reduced GSH and protein-SH content together with diminished SIRT1 activity. The SO-HFD increased TNF-alpha and NO levels. L-arginine supplementation decreased MDA and increased GSH, protein-SH, and SIRT1 activity. L-arginine also suppressed TNF-alpha levels in brain tissue compared to the SO-HFD group. NO levels in the SO-HFD + L-arginine group were lower than in the SO-HFD group, though not significantly.ConclusionThese findings suggest that chronic exposure to an omega-6-dominant dietary environment disturbs redox regulation and inflammatory balance in brain tissue, accompanied by reduced SIRT1 activity. L-arginine may attenuate cerebral oxidative stress and neuroinflammation by reinforcing endogenous antioxidant mechanisms, highlighting its potential as a nutritional strategy against SO-HFD-induced brain oxidative stress.