Plasma ghrelin levels after laparoscopic sleeve gastrectomy in obese individuals

Obesity is one of the leading causes of morbidity and mortality worldwide. The International Association for the Study of Obesity/International Obesity Task Force, a WHO body has reported that approximately one billion adults worldwide are overweight and another 475 million adults are obese1. Laparoscopic sleeve gastrectomy (LSG)2 has gained popularity as a bariatric procedure due to its safety, low complication rate and excellent weight loss results. It is a restrictive procedure, involving resection of the gastric fundus, which expresses various hormones associated with hunger and satiety, insulin secretion and energy balance3. LSG appears to permanently inhibit ghrelin production in majority of individuals within days of surgery which is mainly implicated in high success rates of sleeve gastrectomy in obese individuals45.

Ghrelin is a 28-amino acid peptide produced from the fundus of the stomach and the proximal intestine67 and is the only known orexigenic gut hormone. Central and peripheral administration of this hormone leads to increased food intake8. Ghrelin levels increase before meals and are suppressed postprandially in proportion to the amount of calories ingested, therefore, suggesting a possible role in meal initiation89. Ghrelin stimulates appetite, increases gastric motility and secretion, increases growth hormone secretion and reduces fat utilization789. A 24 h profile of ghrelin increases following diet-induced weight loss supporting the hypothesis that ghrelin has a role in the long-term regulation of body weight10. A few investigators have assessed the change in fasting ghrelin levels after LSG4511. A prospective, double-blind study comparing Roux-en-Y Gastric bypass (RYGB) and LSG confirmed a significant postprandial suppression of ghrelin postoperatively in LSG group while there was no change in the RYGB group12. Only temporary effects on postoperative plasma ghrelin levels were found by Adami et al13 in patients who underwent biliopancreatic diversion including sleeve gastrectomy. Schindler et al14 showed an increase in fasting ghrelin accompanied by a paradoxical decrease in hunger after LSG suggesting that weight loss was independent of circulating plasma ghrelin. Thus, the exact role of ghrelin in the pathophysiology of obesity is still under investigation and the establishment of exact correlation between LSG, ghrelin and obesity could be vital for the fight against obesity. The aim of this study was to evaluate the effects of LSG on plasma ghrelin levels and its role in sustainable weight loss in obese patients.

Material & Methods

A total of 90 consecutive patients (52 women and 38 men) aged 24-68 yr who underwent LSG in Dayanand Medical College and Hospital, Ludhiana, India, were enrolled in the study, conducted from August 2013 to June 2015. These included morbidly and severely obese individuals who were suffering from diabetes, hypertension, dyslipidaemia or any one of these diseases. Patients with a history of any bariatric surgical procedure, any terminal illnesses including advanced cancer or end-stage renal, hepatic and cardiopulmonary disease were excluded. Ethical clearance for the study was obtained from the institutional ethics committee and informed written consent were sought from all participants.

Surgical technique: A point on the greater curvature and on the antrum was taken as the starting point (2 to 10 cm from the pylorus). The lesser sac was entered by opening the gastrocolic ligament. The short gastric vessels and the greater curvature ligaments (gastrosplenic and gastrocolic) were divided by ultrasonic dissection to the left crus. A 32 French bougie was passed transorally into the pylorus, placed against the lesser curvature and then a laparoscopic stapler was introduced along the length of the bougie. Stomach was separated and removed with the help of ports15. A drain was then placed along the stapler line.

The patients were subjected to follow up for six months postoperatively and weight loss parameters such as body mass index (BMI) were measured. Fasting plasma ghrelin levels were also measured using the enzyme-linked immunosorbent assay (ELISA)16. Fasting venous blood samples (1 ml) were collected in pre-chilled tubes-containing aprotinin/ethylenediaminetetraacetic acid (EDTA) solution preoperatively on day 1 of hospital admission, one week, three and six months following the operation and the samples were analyzed for plasma ghrelin levels using ELISA kit (Ghrelin EIA kit-sigma RAB0207 Merck KGaA, Darmstadt, Germany).

Statistical analysis was performed to compare the means among the groups using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 20.0. Armonk, NY, USA). A one-way repeated measures analysis of variance (ANOVA) was conducted to evaluate the null hypothesis that there was no change in the plasma ghrelin levels pre- and postoperatively at one week, three months and six months following LSG.

Results & Discussion

A total of 90 patients (mean age 46.27±11.17 yr) were included in the study. Mean height and mean weight were 1.614±0.105 m and 131.24±15.42 kg, respectively. Mean BMI was 49.25±3.96 kg/m²Z. BMI and weight loss showed a significant reduction in three months which sustained until six months postoperatively (P<0.001).

A one-way repeated measures ANOVA was conducted to evaluate the null hypothesis that there was no change in the plasma ghrelin levels pre- and postoperatively at one week, three and six months following LSG in obese patients. There was a significant decrease in plasma ghrelin levels at one week, three months and six months postoperatively following LSG (P<0.001) compared to pre-operative levels (Table).

Alterations of orexigenic hormone ghrelin play an important role in appetite fluctuation and preservation of achieved weight reduction following bariatric surgery1517. Various factors play a role in causing weight loss following LSG such as decreased gastric capacity, decreased gastric emptying time and reduced ghrelin levels postoperatively18. In our study, the mean weight loss and BMI following LSG at one week, three and six months postoperatively were significant (P<0.001) (Table). Gluck et al19 also reported similar results. This was also in concordance with other studies45.

Being a short-term follow up this study may not reflect long-term effects on weight loss produced by LSG. The sample size was also small. The findings need to be studied on a larger group before these can be standardized and recommended.

In conclusion, a significant decrease in fasting plasma ghrelin levels was seen after LSG, a surgical intervention for treatment of morbid obesity, which began as early as the first week and remained till six months postoperatively. A significant weight loss and reduction in BMI following the surgery were also observed.