Is Ghrelin the Culprit for Weight Loss after Gastric Bypass Surgery? A Negative Answer

Background: Ghrelin is a potent appetite stimulator, mainly synthesized in the stomach. Paradoxically, obese subjects have lower plasma ghrelin than lean subjects and increase their weight in spite of low ghrelin levels. The role of ghrelin in weight regulation after bariatric surgery is still controversial. The aim of this study was to evaluate whether rapid weight loss after laparoscopic Roux-en-Y gastric bypass surgery (LRYGBP), was associated with changes in plasma ghrelin levels. In addition, we determined the acute impact of LRYGBP on insulin resistance and adiponectin levels. Methods: 49 morbidly obese subjects who underwent LRYGBP were studied. 19 subjects who underwent other laparoscopic gastrointestinal surgeries acted as the control group. Fasting plasma levels of ghrelin, insulin and adiponectin were determined preoperatively and 2 hours, 10 days and 6 months postoperatively. Results: At 2 hours after LRYGBP, there was a significant reduction in ghrelin and adiponectin levels, which coincided with elevated plasma glucose and insulin levels. Interestingly, once glucose and insulin levels normalized at 6 months after surgery, ghrelin also normalized. Adiponectin reached pre-surgical levels at 10 days after LRYGBP and continued to significantly rise until 6 months postoperatively. Conclusion: Weight loss after LRYGBP occurs in spite of the absence of significant changes in plasma ghrelin levels. Improvement of insulin resistance occurred within 10 days after surgery, and could be related to the normalization of adiponectin levels. This data questions the role of peripheral ghrelin as a cause of weight loss in obese humans after LRYGBP.