Long‐Term Intake of Oleic Acid‐Rich Palm Oil Induces Obesity Without Impairing Hypothalamic Insulin Sensitivity and Redox Activity in Male Wistar Rats

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Abstract
The debate over the impact of extensive palm oil consumption on human health, driven by its economic affordability, persists due to its high saturated fat content and potential health risks. Conversely, its diverse bioactive compounds offer antioxidant and anti‐inflammatory properties. This study seeks to investigate the effects of prolonged palm oil consumption on hypothalamic insulin signaling, inflammation, and oxidative stress markers. Rats were fed either standard chow or a palm oil‐enriched diet (POD) for 21 weeks, with the latter diet prepared by soaking standard briquette food in commercially available palm oil. The palm oil used in our study contained slightly more oleic acid than palmitic acid (44.3% and 39.5%, respectively). Prolonged consumption of a diet enriched with 20% of palm oil resulted in obesity in rats, accompanied by concurrent changes in blood lipid content. Additionally, palm oil consumption induced hyperinsulinemia and hyperglycemia, indicating the presence of peripheral insulin resistance. Despite these findings, our study did not reveal differences in hypothalamic insulin resistance between obese and control rats. In the cerebrospinal fluid, insulin concentration remained consistent after palm oil consumption, while glucose levels increased. Hypothalamic gene expression analysis did not show significant changes in the levels of NF‐κB, IL‐6, IL‐1β, and Nrf2 mRNA. Moreover, the activation of insulin receptor and its substrate IRS1, as well as the expression of glucose transporters GLUT1‐4 in the rat hypothalamus, remained unaltered. Ex vivo EPR spectroscopy of the obese rat hypothalamus indicated no variations in the total redox status compared to control rats. In summary, our results suggest that long‐term consumption of palm oil rich in oleic acid induces obesity but does not significantly impact hypothalamic insulin expression and response, inflammation, or oxidative stress, which at least in part may be attributed to the specific fatty acid composition of the palm oil used. However, the potential contribution of other phytochemicals and bioactive compounds, such as vitamin E, must not be overlooked when interpreting the overall metabolic response to the prolonged palm oil intake.

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