Our goal was to assess changes of gut peptides after short-term weight loss by 2 different methods, diet and GBP surgery. We wished to elucidate possible hormonal mechanisms of energy homeostasis responsible for the greater efficacy of GBP compared with diet.
The main result of this study is that PYY3–36
levels increased markedly in response to oral glucose after GBP surgery, but not after an equivalent weight loss by diet. These results confirm previous data from cross-sectional6,8
studies showing increased gut peptide levels after GBP or jejuno-ileal bypass.23
Our data demonstrate that weight loss alone does not contribute to the changes in PYY levels observed after GBP, as stimulated PYY3–36
levels did not increase after a diet-induced weight loss. To our knowledge, these are the first data on stimulated PYY3–36
level after diet-induced weight loss. Similarly to our results after diet, PYY levels do not increase after purely restrictive surgeries such as gastric banding,8,24
although they increase after vertical banded gastroplasty.25
The mechanism by which stimulated PYY levels increase after GBP could be related to the more rapid delivery of nutrients, as intestinal transit time is accelerated after GBP7
and as suggested by studies after ileal transposition in rats.26
In our study, fasting PYY3–36
levels decreased after GBP but did not change after diet. These findings are in contrast to those of Roth et al,13
who showed that diet-induced weight loss in obese children increased fasting PYY levels and of Pfluger et al,14
who showed a decrease in fasting PYY levels after diet in adults. Discrepancies between studies could be related to age, sex, diabetes status, and/or energy balance differences.
PYY is rapidly cosecreted with GLP-1 from intestinal L-cells in response to food intake.27,28
have shown a marked increase in GLP-1 levels in response to oral glucose or a meal after GBP. The administration of PYY3–3630
or of GLP-131–34
reduces food intake in lean and in obese human individuals. GLP-1 and PYY infused simultaneously lower food intake more than either peptide administered alone in lean and obese rodents and in lean humans.35
The increase in the levels of these 2 anorexigenic peptides in concert with the decrease in the orexigenic peptide ghrelin, may act together with pancreatic and adipose hormones to inhibit energy intake and favor weight loss after GBP.12
Examples of these interactions have been demonstrated in rats: ghrelin attenuates, dose-dependently, the anorectic effect of PYY and GLP-1,36
and the coadministration of leptin with PYY3–36
enhances the anoretic effects of PYY3–36
The compensatory increase in ghrelin levels after diet-induced weight loss was not observed after GBP. Although conflicting results on the changes in plasma ghrelin after GBP have been reported,6,18,24,38–43
most studies agree that ghrelin levels either decrease or do not increase in proportion to the amount of weight loss after GBP surgery. Ghrelin15,44
and ghrelin analogs45,46
stimulate food intake in lean and obese humans and increase body weight and adiposity in rodents.15
The increase in ghrelin levels after diet may play a role in weight regain and explain, in part, the lower effectiveness of diet for sustained weight loss compared with GBP.
Despite similar weight loss, leptin levels decreased more after GBP than after diet, although this did not reach statistical significance. Others have found lower leptin levels after GBP surgery compared with a BMI-matched group.24
The relatively low levels of leptin after GBP may indicate that factors other than the change in adipose mass may be responsible for the decrease in circulating leptin concentration after GBP. In our study, the level of energy restriction could account for variability in the decrease in leptin levels after GBP and diet.21
Different patterns in gut and pancreatic hormones resulting from GBP could also play a role in the regulation of plasma leptin levels. In vitro, ghrelin stimulates the differentiation of preadipocytes47
and inhibits adipocyte apoptosis.48
The fall of ghrelin levels after GBP could alter its effect on adipose tissue and modulate circulating leptin levels. In addition, leptin is not only produced by adipose tissue but also in small amounts by the stomach,49
which is altered after surgery.
We found higher fasting and postprandial PYY3–36
levels in obese with T2DM compared with obese without T2DM. English et al also reported that fasting PYY levels were significantly higher in T2DM than in controls.50
However, other studies reported low fasting PYY plasma levels in first-degree relatives of subjects with T2DM51
and blunted postprandial PYY levels in early stages of T2DM development in genetically susceptible individuals.52
It is unclear whether PYY levels contribute to the pathogenesis of T2DM and/or whether glucose homeostasis modulates circulating PYY levels. As previously reported,50
we did not find significant correlation between PYY levels and markers of insulin secretion or sensitivity. Future larger studies are needed to clarify the role of PYY, if any, in the physiopathology of T2DM. As shown by others,6,18,24,39–43,53
diabetes status had no effect on leptin or ghrelin levels.
Our study has some limitations. The small amount of glucose administered in our study (50 g glucose, 200 Kcal) may have been insufficient to stimulate PYY3–36
release before weight loss intervention. PYY release is influenced by amount of calories54
and the nutrient composition of the meal, with dietary carbohydrates being weaker stimulants of PYY than protein or fat.27,55–57
However, the same stimulus was able to markedly increase PYY3–36
levels after GBP to levels that could contribute to higher postprandial satiety and weight loss after GBP. Oral glucose is a clinical research tool, used by diabetologists, that reflects poorly on daily food intake. Whether the large increase in PYY levels after oral glucose has any clinical relevance under conditions of normal feeding will remain to be determined. Another limitation of our study is the lack of measurement of hunger or satiety ratings of ad libitum food intake. However, the changes in circulating levels of peptides implicated with meal-to-meal regulation correlates poorly with quantified measures of hunger after GBP6,58
and ad libitum food intake is difficult to study in the early stages after GBP. Another limitation is the absence of perfect matching in calorie restriction between the GBP and the diet group. The diet arm was designed to match the weight loss of the GBP group, not their calorie intake. However, the overall calorie deficit and weight loss were identical.
In summary, we show that the increase in PYY3–36 levels after GBP, but not after diet-induced weight loss, results from the surgical procedure, independently of weight loss. The changes of PYY3–36, ghrelin, and leptin levels, all important regulators of food intake and energy homeostasis, may explain, in part, the greater effectiveness of GBP in sustaining weight loss compared with diet. Understanding the mechanisms involved in the changes of these peptides after the surgery could lead to new treatments for obesity and related metabolic conditions.