This study investigates the relationship between plasma ghrelin levels and weight loss, both through diet-induced weight loss and gastric bypass surgery. The researchers measured 24-hour plasma ghrelin profiles, body composition, insulin levels, leptin levels, and insulin sensitivity in obese subjects before and after a six-month dietary program for weight loss. They also compared these profiles with those of subjects who had lost weight through gastric bypass surgery and normal-weight controls. Key findings include: - **Diet-Induced Weight Loss:** Plasma ghrelin levels increased by 24% after diet-induced weight loss, suggesting that ghrelin may play a role in the adaptive response that limits weight loss. - **Gastric Bypass Surgery:** Plasma ghrelin levels were significantly lower in subjects who had undergone gastric bypass compared to normal-weight controls and matched obese controls. The gastric-bypass group showed no meal-related fluctuations or diurnal rhythm in ghrelin levels, indicating a disruption in ghrelin secretion. The study suggests that ghrelin may be involved in both mealtime hunger and long-term regulation of body weight. Gastric bypass surgery, which disrupts the normal gastrointestinal anatomy, may reduce weight by suppressing ghrelin production. These findings provide insights into the mechanisms underlying weight loss and suggest that ghrelin antagonists could potentially be used in the treatment of obesity.This study investigates the relationship between plasma ghrelin levels and weight loss, both through diet-induced weight loss and gastric bypass surgery. The researchers measured 24-hour plasma ghrelin profiles, body composition, insulin levels, leptin levels, and insulin sensitivity in obese subjects before and after a six-month dietary program for weight loss. They also compared these profiles with those of subjects who had lost weight through gastric bypass surgery and normal-weight controls. Key findings include: - **Diet-Induced Weight Loss:** Plasma ghrelin levels increased by 24% after diet-induced weight loss, suggesting that ghrelin may play a role in the adaptive response that limits weight loss. - **Gastric Bypass Surgery:** Plasma ghrelin levels were significantly lower in subjects who had undergone gastric bypass compared to normal-weight controls and matched obese controls. The gastric-bypass group showed no meal-related fluctuations or diurnal rhythm in ghrelin levels, indicating a disruption in ghrelin secretion. The study suggests that ghrelin may be involved in both mealtime hunger and long-term regulation of body weight. Gastric bypass surgery, which disrupts the normal gastrointestinal anatomy, may reduce weight by suppressing ghrelin production. These findings provide insights into the mechanisms underlying weight loss and suggest that ghrelin antagonists could potentially be used in the treatment of obesity.