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This study aimed to investigate the satiety effects of isocalorically replacing carbohydrate energy in a meal with avocado-derived fats and fibers. In a randomized 3-arm, 6-h, crossover clinical trial, thirty-one overweight/obese adults consumed a low-fat control meal (CON, 76% carbohydrate, 14% fat as energy, 5 g fiber, ~640 kcal) or high-fat meals similar in total fat and energy, but increasing avocado-derived fat and fiber content from half (HA, 68 g; 51% carbohydrate, 40% fat as energy, 8.6 g fiber) or whole avocado (WA, 136 g; 50% carbohydrate, 43% fat as energy, 13.1 g fiber) on three separate occasions. Visual analog scales (VAS) assessed subjective satiety over 6 h. Hormones associated with satiety/appetite were measured in blood collected immediately after VAS. Stepwise multiple regression analysis was used to assess the relationship of VAS with hormones in WA and CON. Hunger suppression was enhanced after the WA compared to CON meal (< 0.01). Subjects indicated feeling more satisfied after both HA and WA than CON (< 0.05). Fullness was greater after CON and WA vs. HA (< 0.005). PYY and GLP-1 were significantly elevated after WA vs. CON (< 0.05), while insulin was significantly higher after CON vs. WA (< 0.0001). Ghrelin was suppressed more by CON than WA (< 0.05). Regression analysis indicated PYY was associated with subjective satiety after WA, whereas increased insulin predicted changes in subjective satiety after CON. Replacing carbohydrates in a high-carbohydrate meal with avocado-derived fat-fiber combination increased feelings of satiety mediated primarily by PYY vs. insulin. These findings may have important implications for addressing appetite management and metabolic concerns. View Full-Text