Chronic Consumption of Ghee (Clarified Butter) and Coconut Oil, but Not Palmolein, Induces Microvesicular Steatosis, Insulin Resistance, and Inflammation in Mice Fed a High-Fat Diet

Background/Objectives: A high-calorie diet contributes to the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Excessive saturated fat intake can lead to metabolic dysfunction, depending on the sources, quality, and duration of the oils and fats consumed. Palmolein, ghee, and coconut oil are common dietary fats that differ in saturated fatty acid (SFA) content. However, the impact of these fats on liver steatosis remains unclear. Methods: Forty adult male C57BL/6 mice were divided into five groups (n = 8/group): chow diet (5% w/w peanut oil) and high-fat diets (HFDs) enriched with peanut, palmolein, ghee, and coconut oil (all 25% w/w). Peanut oil, which is a traditional cooking oil, was used as a reference. All the HFD groups were isocaloric and received 58.4% of their energy from fat. Results: After 6 months, bodyweight gain and fasting glucose were elevated in all HFD-fed groups (p < 0.05), except in the peanut oil-fed group. The ghee-fed group showed the highest feed efficiency, visceral adiposity, insulin resistance, plasma triglycerides (TGs), leptin, liver TGs, fatty liver score, interleukin 6 (IL-6) expression, and TBARS levels (p < 0.05). Unlike the ghee-fed group, the coconut oil-fed group exhibited insulin resistance, hepatic lipid accumulation, and IL-6 expression (p < 0.05), independent of visceral adiposity and oxidative stress. The palmolein oil-fed groups showed minimal changes in fatty liver score (p > 0.05) compared with the ghee- and coconut oil-fed groups. Conclusions: In the HFD setup, chronic intake of ghee- and coconut oil-enriched diets induces microvesicular steatosis and inflammation in the liver compared with the peanut and palmolein diets by triggering insulin resistance and dyslipidemia.