To the Editor:
We found the article by le Roux et al very interesting.1 The authors investigated the effect of bariatric surgery on gut hormones secretion, an endocrine response to the bypass of part of the small bowel responsible of glycemic control, appetite reduction, and long-term reduction in body weight.1
To investigate the hormonal changes after Roux-en-Y gastric bypass (RYGB), basal and meal-stimulated secretion of peptide YY, glucagon-like peptide-1 (GLP-1), polypeptide, insulin, leptin and ghrelin were compared with a group of patients undergoing gastric banding and with 2 control groups composed, respectively, by lean and obese subjects.
To further investigate the role of the hormonal response observed in humans, a jejuno-intestinal bypass (JIB) was carried out in Wistar rats of 387 ± 11.7 g.1
The main goal in the animal experiment was to reproduce hormonal changes observed in humans, postulating that these changes are due to the early arrival of nutrients in the terminal ileum as consequence of the bypass of the jejunum, and to demonstrate the role of PYY in reduction of appetite after bariatric procedures entailing with bypass of part of the small bowel. Comparing JIB rats with sham-operated animals, JIB rats experienced a significant postoperative weight loss with a parallel reduction in food intake. Moreover, the authors excluded the presence of malabsorption in the JIB group using a ballistic bomb calorimeter, therefore referring the modifications in body weight and in food intake solely to the hormonal variations.1
We would like to point out some technical obscure aspects of the experimental protocol.
First, if the experiments in the rats aim to reproduce hormonal changes observed in obese humans who underwent RYGB, an obese rat model should be more appropriate.
Differences in gut hormonal secretion were, in fact, described among obese and lean subjects: obese control subjects exhibited an attenuated GLP-1 response to meal and a lack of response to meal of PYY. Fasting ghrelin levels were lower in the obese subjects.1
Therefore, an obese rat model would be more realistic to study the hormonal modifications after the bypass of the small bowel in an experimental setting.
Moreover, JIB does not seem so appropriate as surgical model to reproduce hormonal changes after RYGB without inducing malabsorption. It’s hard to believe that this operation is not malabsorptive, when resection of part of the small bowel is traditionally used in the rat to induce a short bowel syndrome.2
Two reasons may be possible to explain the results obtained with the ballistic bomb calorimetric method: the bypassed small bowel was very short, but no indications are given in the text about the length of the blind loop, or a more detailed stool analysis to determine malabsorption would have been necessary to break down this dogma.3
Other methods to induce the hormonal modifications secondary to the early arrival of food in the ileum are well described, and ileal transposition, in our knowledge, seems to be the more effective, reproducing a hormonal pattern similar to that of RYGB without reducing the bowel length.3–7
The authors assert that JIB is the only established model of bariatric surgery in rodents, omitting the numerous other experimental models described in the literature.2
Another question to the authors is about the technique used to measure GLP-1 plasma levels, which is not mentioned in the paper.
Since GLP-1 is rapidly metabolized in the circulation by the ubiquitous enzyme DPP IV, 2 assays for GLP-1 are available. The former, and most widely used, has been designed for the assay of the intact hormone and its inactive metabolites (total GLP-1), while a second one determines the bioactive form (bioactive GLP-1). The total GLP-1 assay, however, can be used just to trace the secretion rate of the hormone without providing any information about the activity and the amount of circulating bioactive GLP-1. Therefore, antiserum for GLP-17–37 and GLP-17–36amide (bioactive GLP-1) should be preferred to assay modifications in the secretion of this peptide and to evaluate its effects.5,8
Moreover, to verify an effect of JIB on GLP-1 secretion a control group of not operated rats should be necessary. Active GLP-1, indeed, was significantly higher in plasma of rats undergone ileal transposition in respect to sham-operated rats but not to a group of not operated rats during a period of 15 minutes after an oral gavage of glucose 1 g/kg,5 and data are confirmed in the same surgical model in a period of 120 minutes after glucose load (data not published). Therefore, some factor influencing GLP-1 secretion linked to the small bowel division must be taken into account in this type of research.
The human study probably suffers of a type 2 error and cannot be considered definitive about GLP-1 modifications after RYGB, and once again the form of GLP-1 assayed is not indicated in the text.
Alberto Patriti, MD
Enrico Facchiano, MD
Nino Gullà, MD
Department of Surgery
University of Perugia
Perugia, Italy
albertopatriti@alice.it
Maria Cristina Aisa, PhD
Claudia Annetti
Department of Internal Medicine
University of Perugia
Perugia, Italy
albertopatriti@alice.it
REFERENCES
- 1.le Roux CW, Aylwin SJ, Batterham RL, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243:108–114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Del Castillo Dejardin D, Sabench Pereferrer F, Hernandez Gonzalez M, et al. The evolution of experimental surgery in the field of morbid obesity. Obes Surg. 2004;14:1263–1272. [DOI] [PubMed] [Google Scholar]
- 3.Strader AD, Vahl TP, Jandacek RJ, et al. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab. 2005;288:E447–E453. [DOI] [PubMed] [Google Scholar]
- 4.Mason EE. Ileal [correction of ilial] transposition and enteroglucagon/GLP-1 in obesity (and diabetic?) surgery. Obes Surg. 1999;9:223–228. [DOI] [PubMed] [Google Scholar]
- 5.Patriti A, Facchiano E, Annetti C, et al. Early improvement of glucose tolerance after ileal transposition in a non-obese type 2 diabetes rat model. Obes Surg. 2005;15:1258–1264. [DOI] [PubMed] [Google Scholar]
- 6.Patriti A, Facchiano E, Sanna A, et al. The enteroinsular axis and the recovery from type 2 diabetes after bariatric surgery. Obes Surg. 2004;14:840–848. [DOI] [PubMed] [Google Scholar]
- 7.Patriti A, Facchiano E, Donini A. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004;240:388–389; author reply 389–391. [DOI] [PMC free article] [PubMed]
- 8.Vilsboll T, Krarup T, Deacon CF, et al. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001;50:609–613. [DOI] [PubMed] [Google Scholar]