This study examines the changes in plasma ghrelin levels after diet-induced weight loss and gastric bypass surgery. Ghrelin, a hormone produced primarily by the stomach, increases appetite and food intake. The study found that diet-induced weight loss of 17% of initial body weight was associated with a 24% increase in the area under the curve for the 24-hour ghrelin profile (P=0.006). In contrast, after gastric bypass surgery, despite a 36% weight loss, the area under the curve for the ghrelin profile was 77% lower than in normal-weight controls (P<0.001) and 72% lower than in matched obese controls (P=0.01). The normal meal-related fluctuations and diurnal rhythm of ghrelin levels were absent after gastric bypass. The study suggests that ghrelin may play a role in the long-term regulation of body weight. Gastric bypass surgery is associated with markedly suppressed ghrelin levels, which may contribute to its weight-reducing effect. The findings indicate that ghrelin levels increase with diet-induced weight loss, consistent with the hypothesis that ghrelin is involved in the adaptive response to weight loss. However, gastric bypass surgery leads to significantly lower ghrelin levels, possibly due to the isolation of ghrelin-producing cells from ingested nutrients. This suppression of ghrelin may contribute to the long-term weight loss observed after gastric bypass surgery. The study also highlights that gastric bypass surgery leads to reduced hunger and altered eating behavior, suggesting that mechanisms beyond gastric restriction are involved in the weight loss effect of the procedure. These findings suggest that ghrelin antagonists may be a potential treatment for obesity.This study examines the changes in plasma ghrelin levels after diet-induced weight loss and gastric bypass surgery. Ghrelin, a hormone produced primarily by the stomach, increases appetite and food intake. The study found that diet-induced weight loss of 17% of initial body weight was associated with a 24% increase in the area under the curve for the 24-hour ghrelin profile (P=0.006). In contrast, after gastric bypass surgery, despite a 36% weight loss, the area under the curve for the ghrelin profile was 77% lower than in normal-weight controls (P<0.001) and 72% lower than in matched obese controls (P=0.01). The normal meal-related fluctuations and diurnal rhythm of ghrelin levels were absent after gastric bypass. The study suggests that ghrelin may play a role in the long-term regulation of body weight. Gastric bypass surgery is associated with markedly suppressed ghrelin levels, which may contribute to its weight-reducing effect. The findings indicate that ghrelin levels increase with diet-induced weight loss, consistent with the hypothesis that ghrelin is involved in the adaptive response to weight loss. However, gastric bypass surgery leads to significantly lower ghrelin levels, possibly due to the isolation of ghrelin-producing cells from ingested nutrients. This suppression of ghrelin may contribute to the long-term weight loss observed after gastric bypass surgery. The study also highlights that gastric bypass surgery leads to reduced hunger and altered eating behavior, suggesting that mechanisms beyond gastric restriction are involved in the weight loss effect of the procedure. These findings suggest that ghrelin antagonists may be a potential treatment for obesity.