Author(s): ZHANG, T., ZU, Y., MIKHAEL, M., SCOGGIN, S., MOUSTAID-MOUSSA, N., YEO, D., LIU, T., ZHANG, Y., KANG, C., JI, L.L., Institution: UNIVERSITY OF THE PACIFIC, Country: UNITED STATES, Abstract-ID: 1814

INTRODUCTION:
Diets high in saturated fat promote obesity, chronic inflammation, dysregulated lipid metabolism, and endoplasmic reticulum (ER) stress in metabolically active tissues, including liver and visceral adipose tissue (VAT). Extra-virgin olive oil (EVOO), rich in Oleocanthal and Oleacein, exhibits antioxidant and anti-inflammatory effects and protects skeletal muscle mitochondrial function when combined with endurance training during high-fat feeding. However, whether EVOO phenolic content exerts dose-dependent protection in liver and VAT, and whether endurance exercise further enhances these effects, remains unclear. This study examined the independent and combined effects of EVOO phenolics and endurance exercise on metabolic dysfunction induced by a high-fat diet (HFD).
METHODS:
60 Female Sprague–Dawley rats (4 weeks old) completed a 12-week intervention and were assigned to HFD (43% kcal from milk fat), HFD supplemented with low-phenolic EVOO (100 mg/L Oleocanthal/Oleacein; LO), LO plus endurance exercise (LO+E), HFD supplemented with high-phenolic EVOO (1000 mg/L Oleocanthal/Oleacein; HO), or HO plus exercise (HO+E). Plasma total cholesterol and TNF-α were measured by ELISA. Liver and VAT were collected for gene expression analyses of lipid metabolism (acetyl-CoA carboxylase [ACC], fatty acid synthase [FASN], carnitine palmitoyltransferase-2 [CPT2]), inflammatory markers (IL-6, TNF-α, MCP-1), anti-inflammatory markers (IL-10, Arg1), and ER stress markers (immunoglobulin heavy chain-binding protein [BiP], C/EBP homologous protein [CHOP]). Data were analyzed using one-way ANOVA.
RESULTS:
HFD significantly increased plasma total cholesterol and TNF-α, which were attenuated by EVOO supplementation and endurance exercise (HFD vs LO+E and HO+E, p<0.05). In the liver, IL-6 expression was reduced in LO and HO groups in a dose-dependent manner compared with HFD, with the greatest reduction observed in HO+E (p=0.015). Combined high-phenolic EVOO and exercise further reduced lipogenic signaling (ACC; p=0.015) and increased fatty acid oxidation markers (CPT2; trend p=0.08). ER stress markers BiP and CHOP were reduced by exercise, with significant effects observed only in the high-phenolic EVOO group (HO vs HO+E, p<0.05). In VAT, endurance exercise reduced MCP-1 and TNF-α in the LO group (LO vs LO+E, p<0.05), while high-phenolic EVOO reduced TNF-α expression (LO vs HO, p<0.01). Arg1 expression was higher in the LO group than in HFD (p < 0.05) but decreased in the corresponding exercise group (LO+E, p < 0.01). CHOP expression was reduced by endurance exercise in the LO group (LO+E vs LO, p<0.05).
CONCLUSION:
High-phenolic EVOO provides dose-dependent protection against HFD-induced metabolic dysfunction, with endurance exercise conferring additive benefits. Together, EVOO phenolics and exercise improve lipid metabolism, reduce inflammation, and alleviate ER stress in both liver and VAT, supporting their combined use as complementary strategies to prevent obesity-related metabolic disease.