1644-P: The Dose Makes the Poison—High-Fat Diet Based on Extra Virgin Olive Oil Leads to Increased Liver Lipogenesis and Glucose Intolerance in Mice

Background & Objectives: Extra virgin olive oil (EVOO) has garnered attention for its potential anti-inflammatory and oxidative properties. However, the effect on metabolic health remains inconclusive. We previously showed that high-fat diets (HFD) based on coconut oil or lard led to glucose intolerance and inflammatory changes in gut and adipose tissue (AT). Our study aimed to investigate the metabolic and immunological consequences of an EVOO-based HFD compared to a HFD based on coconut oil.

Methods: Male mice aged 5-8 weeks were fed a coconut or EVOO-based HFD (Coco HFD, EVOO HFD) or control diet for 1 week, after which the mice underwent glucose and insulin tolerance tests. Flow cytometry was used to characterize immune cells of the colon, AT, and liver. Total liver lipids were determined by a sulfophosphovanillin reaction. qPCR was used for relative DNA quantification. Statistical analysis was performed using ordinary one-way ANOVA with multiple comparisons.

Results: Both HFDs induced hyperinsulinemia, but the EVOO HFD led to pronounced glucose intolerance and insulin resistance. Furthermore, mice fed an EVOO HFD had significantly elevated total liver lipids and increased expression of lipogenesis genes, particularly Srebp1c. However, mice on EVOO HFD showed partial protection from inflammation in the AT and colon. Neither of the HFDs resulted in systemic inflammation after 1 week.

Conclusion: Our study highlights specific metabolic and immune responses induced by different dietary fat sources. Importantly, although EVOO HFD has fewer pro-inflammatory properties compared to Coco HFD, it results in pronounced glucose intolerance. This may be related to increased hepatic lipogenesis and subsequent elevation of hepatic lipids, possibly induced by oleic acid, which accounts for approximately 70 % of EVOO.