Ghrelin and Adipose Tissue Regulatory Peptides: Effect of Gastric Bypass Surgery in Obese Humans

Abstract

Presently surgery is the most effective way to obtain a controlled weight reduction in morbidly obese patients. Roux-en-Y gastric bypass (RYGBP) surgery is effective and used worldwide, but the exact mechanism of action is unknown. The effect of RYGBP on ghrelin, insulin, adiponectin, and leptin levels was investigated in 66 obese subjects; mean weight 127 kg (range, 96-195 kg) and mean body mass index (BMI) 45 kg/m(2) (range, 33-64) before and after surgery. Ghrelin levels were also compared in 10 nonoperated and 10 operated obese, BMI-matched women. RYGBP resulted in 22% and 30% weight loss at 6 and 12 months, respectively. Ghrelin increased by 44% and 62% and adiponectin by 36% and 98%, but insulin declined by 57% and 62% and leptin by 60% and 64%. The changes were all related to the reduction in BMI. In addition, ghrelin and insulin were inversely correlated at all time points as were changes of the peptides at 12 months (F = 4.9, P = 0.031), independent of the change in BMI. No evidence for RYGBP surgery per se having an effect on ghrelin levels, independent of weight loss, was obtained. The profound changes in the regulatory peptides are likely to reflect the new state of energy balance achieved. A close inverse association between ghrelin and insulin was observed, supporting an important role for ghrelin in glucose homeostasis.

Meal suppression of circulating ghrelin is normalized in obese individuals following gastric bypass surgery

“…In the present cross-sectional study, we found higher fasting, morning ghrelin levels in the RYGBP group than in the age-matched morbidly obese, which is in accordance with our previous prospective study in 66 patients before and after gastric bypass. 22 Furthermore, after the extended fast we demonstrated a comparable mealrelated suppression of ghrelin concentrations in the middleaged RYGBP group as in the young non-obese group and a tendency to even larger suppressibility in the operated patients compared to the age-matched non-obese subjects, despite a higher BMI in the RYGBP patients. Explanations for these discrepancies between studies might be differences in magnitude of weight loss or differences in surgical procedures.…”

“…7,36 In our previous study, we demonstrated a close inverse association between the circulating concentrations of insulin and ghrelin both preoperatively and 6 and 12 months after gastric bypass. 22 In a study in 10 volunteers, postprandial suppression of plasma ghrelin level was shown to be proportional to ingested caloric load who were given liquid meals with widely varied caloric content. 37 As expected, they also found that the ingested caloric load was directly proportional to the area under the curve of plasma insulin.…”

“…In contrast, we observed increased ghrelin levels in 40 out of 53 patients and in 60 out of 66 patients 6 and 12 months after gastric bypass surgery, respectively. 22 Subsequently, another study reported increased ghrelin levels in subjects undergoing active weight loss after gastric bypass, but not in weight-stable subjects. 23 One explanation for these divergent results could be that surgical techniques may affect the vagus nerve differently, as suggested in an editorial by Cummings and Shannon, 24 as studies in rodents 25 and humans 26,27 have shown that the vagus nerve is essential for ghrelin release.…”

Ghrelin in obesity and endocrine diseases

“…Increases in ghrelin levels post-gastric bypass have also been seen (Garcia-Fuentes et al, 2008;Holdstock et al, 2003;Perez-Romero et al, 2010;Ybarra et al, 2009); however this may be associated with active weight loss rather than the surgery itself (Faraj et al, 2003). Several explanations have been proposed for the conflicting findings regarding ghrelin levels following gastric bypass surgery including differences in pre-operative insulin resistance, surgical methods and post-operative vagal nerve dysfunction (Pournaras & le Roux, 2010;Vincent & le Roux, 2008).…”

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

“…10 The medical treatment of obesity, in particular morbid obesity (BMI Z40 kg/m 2 ), is unsatisfactory and has led to the increased use of surgery worldwide. 11 Roux-en-Y gastric bypass (RYGBP) causes a marked reduction in adipose tissue mass, 12 alters adipose tissue regulatory hormones 13 and reduces morbidity. 14 The changes in body weight and metabolic balance provide a useful study group from which we can examine interactions between obesity, insulin resistance (as indicated by a high HOMA index; ie.…”